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1
Vallejo, Abigail, Belal Chami, Joanne Dennis, Martin Simone, Gulfam Ahmad, Adrian Abdo, Arpeeta Sharma та ін. "NFκB Inhibition Mitigates Serum Amyloid A-Induced Pro-Atherogenic Responses in Endothelial Cells and Leukocyte Adhesion and Adverse Changes to Endothelium Function in Isolated Aorta". International Journal of Molecular Sciences 20, № 1 (28 грудня 2018): 105. http://dx.doi.org/10.3390/ijms20010105.
Повний текст джерелаАнотація:
The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFκB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFκB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 μM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and Tumor Necrosis Factor (TNF) increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and interleukin 6 (IL-6) protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cyclic guanosine monophosphate (cGMP) content. Together these data suggest that inhibition of NFκB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.
2
Hsia, Chih-Wei, Wei-Chieh Huang, Chih-Hao Yang, Chih-Hsuan Hsia, Thanasekaran Jayakumar, Periyakali Saravana Bhavan, Joen-Rong Sheu та Kuan-Rau Chiou. "Comparison of the Potency of Pterostilbene with NF-κB Inhibitors in Platelet Activation: Mutual Activation by Akt-NF-κB Signaling in Human Platelets". Applied Sciences 11, № 13 (2 липня 2021): 6149. http://dx.doi.org/10.3390/app11136149.
Повний текст джерелаАнотація:
Myocardial infarction and cerebral ischemic stroke are prominent causes of death worldwide. Platelets play major roles in these diseases, although they are anucleated cells, but also express the NF-κB. Pterostilbene (PTE) possesses some intriguing pharmacological properties, including the capacity to inhibit platelet activation. We investigated the inhibitory role of PTE in NF-κB-mediated signal events and compared the relative potency with that of classical NF-κB inhibitors. PTE and IκB kinase (IKK) inhibitor, BAY11-7082, and proteasome inhibitor, Ro106-9920, inhibited platelet aggregation; the activity of BAY11-7082 and PTE were similar, but Ro106-9920 was weak in this reaction. PTE and BAY11-7082 diminished NF-κB signaling molecules, including IKK, IκBα, and p65 phosphorylation, and reversed IκBα degradation. However, Ro106-9920 was only effective in diminishing p65 phosphorylation and reversing IκBα degradation. In investigating the role of Akt and NF-κB in cell signaling events, MK-2206 (an inhibitor of Akt) markedly abolished IKK and p65 phosphorylation; BAY11-7082 also reduced Akt phosphorylation. PTE exhibited more potent activity in vivo than did BAY11-7082 in acute pulmonary thromboembolism. In conclusion, we identified a distinctive activation pathway of NF-κB and Akt involved in PTE-mediated antiplatelet aggregation, and PTE demonstrated powerful activity as a prophylactic and as clinical therapy for cardiovascular diseases.
3
Huang, Wei-Chieh, Shaw-Min Hou, Ming-Ping Wu, Chih-Wei Hsia, Thanasekaran Jayakumar, Chih-Hsuan Hsia, Periyakali Saravana Bhavan, Chi-Li Chung та Joen-Rong Sheu. "Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB". Molecules 27, № 2 (12 січня 2022): 476. http://dx.doi.org/10.3390/molecules27020476.
Повний текст джерелаАнотація:
Platelets play a critical role in arterial thrombosis. Rutaecarpine (RUT) was purified from Tetradium ruticarpum, a well-known Chinese medicine. This study examined the relative activity of RUT with NF-κB inhibitors in human platelets. BAY11-7082 (an inhibitor of IκB kinase [IKK]), Ro106-9920 (an inhibitor of proteasomes), and RUT concentration-dependently (1–6 μM) inhibited platelet aggregation and P-selectin expression. RUT was found to have a similar effect to that of BAY11-7082; however, it exhibits more effectiveness than Ro106-9920. RUT suppresses the NF-κB pathway as it inhibits IKK, IκBα, and p65 phosphorylation and reverses IκBα degradation in activated platelets. This study also investigated the role of p38 and NF-κB in cell signaling events and found that SB203580 (an inhibitor of p38) markedly reduced p38, IKK, and p65 phosphorylation and reversed IκBα degradation as well as p65 activation in a confocal microscope, whereas BAY11-7082 had no effects in p38 phosphorylation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay shows that RUT and BAY11-7082 did not exhibit free radical scavenging activity. In the in vivo study, compared with BAY11-7082, RUT more effectively reduced mortality in adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism without affecting the bleeding time. In conclusion, a distinctive pathway of p38-mediated NF-κB activation may involve RUT-mediated antiplatelet activation, and RUT could act as a strong prophylactic or therapeutic drug for cardiovascular diseases.
4
Hsia, Chih-Wei, Chih-Hao Yang, Joen-Rong Sheu, Chih-Hsuan Hsia, Cheng-Lin Tsai, Wei-Chieh Huang, Ting-Yu Chen, Thanasekaran Jayakumar, Periyakali Saravana Bhavan та Yi Chang. "Reduction of NF-κB Signals in Platelets and Prolongation of Platelet Plug Formation against High Shear Flow in Whole Blood on Human Subject by Columbianadin". Applied Sciences 10, № 20 (19 жовтня 2020): 7323. http://dx.doi.org/10.3390/app10207323.
Повний текст джерелаАнотація:
Myocardial infarction and cerebral ischemic stroke during the process of arterial thrombosis are prominently causes of death worldwide. Platelets are anucleated cells and play a critical factor in these diseases. Columbianadin (CBN), a coumarin derivative from plants, inhibits effective platelet activation. In this study, platelet function analysis revealed that the closure time of the platelet plug in human whole blood significantly prolonged by CBN, whereas CBN did not pointedly prolong the bleeding time in mice. BAY11-7082 (an inhibitor of IκB kinase) and MG-132 (an inhibitor of proteasome) inhibited collagen-stimulated platelet aggregation and ATP-release in human platelets, BAY11-7082 exhibited a higher potency than MG-132. Moreover, CBN markedly reduced NF-κB activation (e.g., IκBα and p65 phosphorylation) and reversed IκBα degradation in activated platelets. We investigated intercellular signaling events between mitogen-activated protein kinases and NF-κB, and found that BAY11-7082 abolished JNK1/2 and ERK1/2 phosphorylation. Interestingly, SP600125 (an inhibitor of JNK) but not PD98059 (an inhibitor of ERK) had no effect in NF-κB activation in activated platelets. Moreover, CBN but not BAY11-7082 significantly reduced hydroxyl radical (HO●) formation in platelets. Therefore, we propose that CBN inhibits NF-κB activation in human platelets and could present a potent clinical treatment for thromboembolic diseases.
5
Hsia, Chih-Wei, Ming-Ping Wu, Ming-Yi Shen, Chih-Hsuan Hsia, Chi-Li Chung та Joen-Rong Sheu. "Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway". International Journal of Molecular Sciences 21, № 13 (7 липня 2020): 4810. http://dx.doi.org/10.3390/ijms21134810.
Повний текст джерелаАнотація:
Platelets are major players in the occurrence of cardiovascular diseases. Auraptene is the most abundant coumarin derivative from plants, and it has been demonstrated to possess a potent capacity to inhibit platelet activation. Although platelets are anucleated cells, they also express the transcription factor, nuclear factor-κB (NF-κB), that may exert non-genomic functions in platelet activation. In the current study, we further investigated the inhibitory roles of auraptene in NF-κB-mediated signal events in platelets. MG-132 (an inhibitor of proteasome) and BAY11-7082 (an inhibitor of IκB kinase; IKK), obviously inhibited platelet aggregation; however, BAY11-7082 exhibited more potent activity than MG-132 in this reaction. The existence of NF-κB (p65) in platelets was observed by confocal microscopy, and auraptene attenuated NF-κB activation such as IκBα and p65 phosphorylation and reversed IκBα degradation in collagen-activated platelets. To investigate cellular signaling events between PLCγ2-PKC and NF-κB, we found that BAY11-7082 abolished PLCγ2-PKC activation; nevertheless, neither U73122 nor Ro31-8220 had effect on NF-κB activation. Furthermore, both auraptene and BAY11-7082 significantly diminished HO• formation in activated platelets. For in vivo study, auraptene prolonged the occlusion time of platelet plug in mice. In conclusion, we propose a novel inhibitory pathway of NF-κB-mediated PLCγ2-PKC activation by auraptene in human platelets, and further supported that auraptene possesses potent activity for thromboembolic diseases.
6
Tzao, Ching, Li-Yuan Cheng, Chien-Chih Chang та Guang-Huan Sun. "The role of NF-κB pathway in cancer inflammation of esophageal squamous carcinoma." Journal of Clinical Oncology 31, № 4_suppl (1 лютого 2013): 42. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.42.
Повний текст джерелаАнотація:
42 Background: Chronic inflammation plays an important role in tumorigenesis and tumor progression in human cancers. We aim to investigate the role of NF-kB in cancer inflammation of esophageal squamous cell carcinoma (ESCC). Methods: To generate M2-polarized macrophages, cells of human U937 monocyte cell line were treated with phorbol myristate acetate (PMA, 50 ng/ml) for 6 hours, and then cultured with PMA plus Th2 cytokines, IL-4 (20 ng/ml) and IL-13 (20 ng/ml), for another 18 hours. M2 phenotype was verified by flow cytometry and by cytokine profiling using enzyme-linked immunosorbent assay (ELISA). After co-culture with M2 macrophages, transcription nuclear factor-kB (NF-kB) activity was measured using quantitative polymerase chain reaction (Q-PCR), followed by reconfirmation with Western blot analysis for IkBα in KYSE-170 and -510 ESCC cell lines (kindly provided by Dr. Yutaka Shimada at Kyoto University, Japan). A selective inhibitor to NF-kB, Bay11-7082, was used to treat ESCC cell lines co-cultured with M2 macrophages, followed by cell proliferation, migration, invasion assays and vascular endothelial growth factor (VEGF) secretion by ELISA. The effect of Bay11-7082 (5 mg/kg) against growth of ESCC tumor was tested in xenografted tumors. Results: PMA plus Th2 cytokines treatment promoted differentiation of U937 cells into M2 macrophages. When treated with Bay11-7082, proliferation, migration, invasion and induction of VEGF expression was significantly inhibited in M2 macrophage co-cultured ESCC cells with a down-regulation of IkBα expression. Tumor growth was significantly increased in M2 macrophage co-cultured ESCC cells compared to that of the non-co-cultured controls, which was significantly retarded by treatment with Bay11-7082. Conclusions: NF-kB pathway was activated in ESCC cell lines co-cultured with M2 macrophages with an increase in cell proliferation, cell motility and angiogenic factor in vitro and tumor growth in vivo, which were significantly suppressed by a NF-kB inhibitor, Bay11-7082. These results suggest a role of M2 macrophage in promoting aggressiveness of ESCC cells, possibly through an activation of NF-kB pathway that may serve as a potential therapeutic target for ESCC.
7
Guo, Fangming, Yunhua Hu, Qiang Niu, Yu Li, Yusong Ding, Rulin Ma, Xianhua Wang, Shugang Li та Jianxin Xie. "Grape Seed Proanthocyanidin Extract Inhibits Human Esophageal Squamous Cancerous Cell Line ECA109 via the NF-κB Signaling Pathway". Mediators of Inflammation 2018 (17 грудня 2018): 1–12. http://dx.doi.org/10.1155/2018/3403972.
Повний текст джерелаАнотація:
Esophageal squamous cell carcinoma is the most common type of squamous cell carcinoma. Grape seed proanthocyanidin extract (GSPE) is considered to exhibit anticancer activity against several different types of cancer. We aimed to determine whether GSPE inhibited esophageal squamous cancerous cells and the possible involvement of NF-κB in this process. The human esophageal squamous cancer cell line ECA109 was treated with GSPE (0–80 μg/mL) and BAY11-7082 (10 μmol/L) for 12, 24, and 48 h. The MTT assay was used to determine cell proliferation; alterations in cell apoptosis were detected by flow cytometry; levels of inflammatory factors interleukin-6 and cyclooxygenase-2 and apoptotic proteins Bax/Bcl-2 were measured by ELISA; qRT-PCR and western blots were used to examine the activation of caspase-3 and NF-κB signaling. GSPE inhibited the proliferation of ECA109 cells and induced cellular apoptosis in a time- and dose-dependent manner. ELISA results showed that GSPE and BAY11-7082 reduced the secretion of inflammatory cytokines interleukin-6 and cyclooxygenase-2. The results of PCR and western blotting indicated that GSPE and BAY11-7082 activated caspase-3 and attenuated the activation of the NF-κB signaling pathway. GSPE induced apoptosis in ECA109 cells and inhibited ECA109 cell proliferation via a reduction in the secretion of inflammatory cytokines. This mechanism may be related to the attenuation of NF-κB activity and the sensitization of caspase-3.
8
Qiu, Zhen, Shaoqing Lei, Bo Zhao, Yang Wu, Wating Su, Min Liu, Qingtao Meng, Bin Zhou, Yan Leng, and Zhong-yuan Xia. "NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–17. http://dx.doi.org/10.1155/2017/9743280.
Повний текст джерелаАнотація:
The reactive oxygen species- (ROS-) induced nod-like receptor protein-3 (NLRP3) inflammasome triggers sterile inflammatory responses and pyroptosis, which is a proinflammatory form of programmed cell death initiated by the activation of inflammatory caspases. NLRP3 inflammasome activation plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Our present study investigated whether diabetes aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. Type 1 diabetic rat model was established by intraperitoneal injection of streptozotocin (60 mg/kg). MI/R was induced by ligating the left anterior descending artery (LAD) for 30 minutes followed by 2 h reperfusion. H9C2 cardiomyocytes were exposed to high glucose (HG, 30 mM) conditions and hypoxia/reoxygenation (H/R) stimulation. The myocardial infarct size, CK-MB, and LDH release in the diabetic rats subjected to MI/R were significantly higher than those in the nondiabetic rats, accompanied with increased NLRP3 inflammasome activation and increased pyroptosis. Inhibition of inflammasome activation with BAY11-7082 significantly decreased the MI/R injury.In vitrostudies showed similar effects, as BAY11-7082 or the ROS scavenger N-acetylcysteine, attenuated HG and H/R-induced H9C2 cell injury. In conclusion, hyperglycaemia-induced NLRP3 inflammasome activation may be a ROS-dependent process in pyroptotic cell death, and NLRP3 inflammasome-induced pyroptosis aggravates MI/R injury in diabetic rats.
9
Montalbano, Angela Marina, Giusy Daniela Albano, Anna Bonanno, Loredana Riccobono, Caterina Di Sano, Maria Ferraro, Liboria Siena та ін. "Autocrine Acetylcholine, Induced by IL-17A via NFκB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells". Mediators of Inflammation 2016 (2016): 1–16. http://dx.doi.org/10.1155/2016/9063842.
Повний текст джерелаАнотація:
IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh) increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A) to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation), Bay11-7082 (inhibitor of IkBαphosphorylation), Hemicholinium-3 (HCh-3) (choline uptake blocker), and Tiotropium bromide (Spiriva®) (anticholinergic drug) was tested in ourin vitromodel. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.
10
Wang, J., WJ Zhang, W. Xiong, WH Lu, HY Zheng, X. Zhou та J. Yuan. "PM2.5 stimulated the release of cytokines from BEAS-2B cells through activation of IKK/NF-κB pathway". Human & Experimental Toxicology 38, № 3 (25 жовтня 2018): 311–20. http://dx.doi.org/10.1177/0960327118802628.
Повний текст джерелаАнотація:
Previous studies indicated that exposure to fine particulate matter (PM2.5) was related to pulmonary inflammatory diseases through activation of nuclear factor kappa B (NF-κB) signaling pathway to trigger cytokine secretions in human lung carcinoma cells. To investigate the potential mechanisms underlying expression of cytokines via activated NF-κB by PM2.5, human bronchial epithelial cells (BEAS-2B cells) were treated with PM2.5 extracts at different concentrations (6, 13, 25, 50, 100, 200, and 400 µg mL−1) for 6 and 24 h. We found that 100 µg mL−1 PM2.5 increased interleukin 6 (IL-6) and IL-8 expression at 24 h ( p < 0.05 or p < 0.01). Moreover, 100 µg mL−1 PM2.5 upregulated phosphorylated IκB kinase (IKK), p65, and IκBα at 6 h, which could be reversed by the IKK inhibitor Bay11-7082 ( p < 0.05 or p < 0.01). The p65 subunit of NF-κB was translocated into the nucleus of the cells treated with 100 µg mL−1 PM2.5 at 6 and 24 h. Bay11-7082 partly inhibited PM2.5-induced increases of IL-6 and IL-8 secretion. The results indicated that PM2.5 extract increased IL-6 and IL-8 levels in BEAS-2B cells through activation of IKK/NF-κB pathway. Our study will contribute to better understanding of the mechanism of PM2.5-induced pulmonary inflammatory diseases.
11
Zhang, Lingyu, Jing Xie, Ruihuan Gan, Zhangwei Wu, Huatian Luo, Xingyong Chen, Youguang Lu, Lixian Wu та Dali Zheng. "Synergistic inhibition of lung cancer cells by EGCG and NF-κB inhibitor BAY11-7082". Journal of Cancer 10, № 26 (2019): 6543–56. http://dx.doi.org/10.7150/jca.34285.
Повний текст джерела
12
Zhao, Jijun, Hui Zhang, Yuefang Huang, Hongyue Wang, Shuang Wang, Chunmei Zhao, Yingjie Liang та Niansheng Yang. "Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation". International Immunopharmacology 17, № 1 (вересень 2013): 116–22. http://dx.doi.org/10.1016/j.intimp.2013.05.027.
Повний текст джерела
13
Xiao, Lihua, та Yan Chen. "Ulinastatin-Gold Nanoparticles Reduce Sepsis-Induced Cardiomyocyte Apoptosis Through NF-κB Pathway Inactivation". Nanoscience and Nanotechnology Letters 12, № 12 (1 грудня 2020): 1399–405. http://dx.doi.org/10.1166/nnl.2020.3253.
Повний текст джерелаАнотація:
Nanodrug delivery systems have recently become widely studied and applied in the medical field, and nanomaterials have greatly improved drugs’ efficacy. Ulinastatin has been confirmed to inhibit myocardial damage caused by sepsis. However, the effect and mechanism of ulinastatin-gold nanoparticles (UTI-GN) on sepsis-induced cardiomyocyte apoptosis are unknown. Here we explore the effect and mechanism of UTI-GN on sepsis-induced cardiomyocyte apoptosis. Lipopolysaccharide (LPS) was used to stimulate rat cardiomyocytes to construct an in vitro sepsis model. Enzymelinked immunosorbent assay detected cellular inflammatory factors NF-α, IL-1β, and IL-6. Western blots measured iNOS and COX-2 expression. Based on LPS-treated cells, different concentrations of UTI-GN were applied to cardiomyocytes. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) experiments and flow cytometry measured cell viability and apoptosis, respectively. Western blots evaluated apoptotic protein expression of NF-κB, iNOS, and COX-2. The NF-κB pathway inhibitor BAY11-7082 was further used to explore whether UTI-GN played a regulatory role through the NF-κB pathway. LPS promotes NF-α, IL-1β, and IL-6 production and iNOS and COX-2 expression in cardiomyocytes. The results of the MTT experiment showed that UTI-GN has little toxicity to cardiomyocytes. The flow cytometry and western blot experiments showed that UTI-GN promoted cell apoptosis and inhibited NF-κB expression. Additionally, the NF-κB pathway inhibitor BAY11-7082 counteracts the UTI-GN effect. UTI-GN inhibits sepsis-induced cardiomyocyte apoptosis through NF-κB pathway inhibition.
14
Gao, Qi, Yunlong Yang, Yongzhi Feng, Weipeng Quan, Yizhuo Luo, Heng Wang, Jiachen Zheng та ін. "Effects of the NF-κB Signaling Pathway Inhibitor BAY11-7082 in the Replication of ASFV". Viruses 14, № 2 (31 січня 2022): 297. http://dx.doi.org/10.3390/v14020297.
Повний текст джерелаАнотація:
African swine fever virus (ASFV) mainly infects the monocyte/macrophage lineage of pigs and regulates the production of cytokines that influence host immune responses. Several studies have reported changes in cytokine production after infection with ASFV, but the regulatory mechanisms have not yet been elucidated. Therefore, the aim of this study was to examine the immune response mechanism of ASFV using transcriptomic and proteomic analyses. Through multi-omics joint analysis, it was found that ASFV infection regulates the expression of the host NF-B signal pathway and related cytokines. Additionally, changes in the NF-κB signaling pathway and IL-1β and IL-8 expression in porcine alveolar macrophages (PAMs) infected with ASFV were examined. Results show that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8. The NF-κB inhibitor BAY11-7082 inhibited the expression profiles of phospho-NF-κB p65, p-IκB, and MyD88 proteins, and inhibited ASFV-induced NF-κB signaling pathway activation. Additionally, the results show that the NF-κB inhibitor BAY11-7082 can inhibit the replication of ASFV and can inhibit IL-1β and, IL-8 expression. Overall, the findings of this study indicate that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8, and inhibits the replication of ASFV by inhibiting the NF-κB signaling pathway and interleukin-1 beta and interleukin-8 production. These findings not only provide new insights into the molecular mechanism of the association between the NF-κB signaling pathway and ASFV infection, but also indicate that the NF-κB signaling pathway is a potential immunomodulatory pathway that controls ASF.
15
Cahir-McFarland, Ellen D., Kara Carter, Andreas Rosenwald, Jena M. Giltnane, Sarah E. Henrickson, Louis M. Staudt та Elliott Kieff. "Role of NF-κB in Cell Survival and Transcription of Latent Membrane Protein 1-Expressing or Epstein-Barr Virus Latency III-Infected Cells". Journal of Virology 78, № 8 (15 квітня 2004): 4108–19. http://dx.doi.org/10.1128/jvi.78.8.4108-4119.2004.
Повний текст джерелаАнотація:
ABSTRACT Epstein-Barr virus (EBV) latency III infection converts B lymphocytes into lymphoblastoid cell lines (LCLs) by expressing EBV nuclear and membrane proteins, EBNAs, and latent membrane proteins (LMPs), which regulate transcription through Notch and tumor necrosis factor receptor pathways. The role of NF-κB in LMP1 and overall EBV latency III transcriptional effects was investigated by treating LCLs with BAY11-7082 (BAY11). BAY11 rapidly and irreversibly inhibited NF-κB, decreased mitochondrial membrane potential, induced apoptosis, and altered LCL gene expression. BAY11 effects were similar to those of an NF-κB inhibitor, ΔN-IκBα, in effecting decreased JNK1 expression and in microarray analyses. More than 80% of array elements that decreased with ΔN-IκBα expression decreased with BAY11 treatment. Newly identified NF-κB-induced, LMP1-induced, and EBV-induced genes included pleckstrin, Jun-B, c-FLIP, CIP4, and IκBε. Of 776 significantly changed array elements, 134 were fourfold upregulated in EBV latency III, and 74 were fourfold upregulated with LMP1 expression alone, whereas only 28 were more than fourfold downregulated by EBV latency III. EBV latency III-regulated gene products mediate cell migration (EBI2, CCR7, RGS1, RANTES, MIP1α, MIP1β, CXCR5, and RGS13), antigen presentation (major histocompatibility complex proteins and JAW1), mitogen-activated protein kinase pathway (DUSP5 and p62Dok), and interferon (IFN) signaling (IFN-γRα, IRF-4, and STAT1). Comparison of EBV latency III LCL gene expression to immunoglobulin M (IgM)-stimulated B cells, germinal-center B cells, and germinal-center-derived lymphomas clustered LCLs with IgM-stimulated B cells separately from germinal-center cells or germinal-center lymphoma cells. Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signaling pathways further distinguished EBV latency III-infected B cells from IgM-stimulated or germinal-center B cells.
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Fujita, Yuki, Masaaki Nakayama, Mariko Naito, Eiki Yamachika, Tetsuyoshi Inoue, Koji Nakayama, Seiji Iida та Naoya Ohara. "Hemoglobin Receptor Protein from Porphyromonas gingivalis Induces Interleukin-8 Production in Human Gingival Epithelial Cells through Stimulation of the Mitogen-Activated Protein Kinase and NF-κB Signal Transduction Pathways". Infection and Immunity 82, № 1 (14 жовтня 2013): 202–11. http://dx.doi.org/10.1128/iai.01140-12.
Повний текст джерелаАнотація:
ABSTRACTPeriodontitis is an inflammatory disease of polymicrobial origin affecting the tissues supporting the tooth. The oral anaerobic bacteriumPorphyromonas gingivalis, which is implicated as an important pathogen for chronic periodontitis, triggers a series of host inflammatory responses that promote the destruction of periodontal tissues. Among the virulence factors ofP. gingivalis, hemoglobin receptor protein (HbR) is a major protein found in culture supernatants. In this study, we investigated the roles of HbR in the production of inflammatory mediators. We found that HbR induced interleukin-8 (IL-8) production in the human gingival epithelial cell line Ca9-22. p38 mitogen-activated protein kinase (MAPK) and extracellular signal-related kinase 1/2 (Erk1/2) were activated in HbR-stimulated Ca9-22 cells. Inhibitors of p38 MAPK (SB203580) and Erk1/2 (PD98059) blocked HbR-induced IL-8 production. Additionally, HbR stimulated the translocation of NF-κB-p65 to the nucleus, consistent with enhancement of IL-8 expression by activation of the NF-κB pathway. In addition, small interfering RNA (siRNA) targeting activating transcription factor 2 (ATF-2) or cyclic AMP-response element-binding protein (CREB) inhibited HbR-induced IL-8 production. Moreover, pretreatment with SB203580 and PD98059 reduced HbR-induced phosphorylation of CREB and ATF-2, respectively. Combined pretreatment with an inhibitor of NF-κB (BAY11-7082) and SB203580 was more efficient in inhibiting the ability of HbR to induce IL-8 production than pretreatment with either BAY11-7082 or SB203580 alone. Thus, in Ca9-22 cells, the direct activation of p38 MAPK and Erk1/2 by HbR caused the activation of the transcription factors ATF-2, CREB, and NF-κB, thus resulting in the induction of IL-8 production.
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Zhou, Wen, and Xiaoxia Zhu. "Estrogen as Jekyll and Hyde: regulation of cell death." F1000Research 3 (September 29, 2014): 161. http://dx.doi.org/10.12688/f1000research.4753.2.
Повний текст джерелаАнотація:
Sustained estrogenic exposure increases the risk and/or the progression of various cancers, including those of the breast, endometrium and ovary. Unexpectedly, physiological level of estrogen together with a novel IKKα inhibitor BAY11-7082 could effectively induce cell apoptosis in ER-positive breast cancer cells, suggesting combining estrogen with IKKα inhibition may be beneficial for breast cancer patients. This opinion article touches upon the dual role estrogen played in inducing cancer cell death and asks whether use of estrogen in combination with IKKα-targeted therapy would be possible reconsider the newly identified crosstalk between ER and NFκB pathway which can be utilized to switch the effects of estrogen on cell death.
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Corbetta, S., L. Vicentini, S. Ferrero, A. Lania, G. Mantovani, D. Cordella, P. Beck-Peccoz, and A. Spada. "Activity and function of the nuclear factor kappaB pathway in human parathyroid tumors." Endocrine-Related Cancer 12, no. 4 (December 2005): 929–37. http://dx.doi.org/10.1677/erc.1.00970.
Повний текст джерелаАнотація:
Previous studies indicate that nuclear factor kappaB (NF-κB) transcription factor is deregulated and overexpressed in several human neoplasias. The aim of this study was to test the hypothesis that the NF-κB pathway may be involved in parathyroid tumorigenesis. For this purpose, we determined the level of NF-κB activity, evaluated as phosphorylation of the transcription subunit p65, its modulation by specific and non-specific agents and its impact on cyclin D1 expression. Phosphorylated p65 levels present in parathyroid neoplasias (n = 13) were significantly lower than those found in normal tissues (n = 3; mean optical density (OD) 0.19 ± 0.1 vs 0.4 ± 0.1, P = 0.007), but there was no significant difference between adenomas and secondary and multiple endocrine neoplasia type 1 (MEN1)-related hyperplasia. Conversely, MEN2A (Cys634Arg)-related parathyroid samples showed extremely high levels of phosphorylated p65 that exhibited a nuclear localization at immunohistochemistry (n = 3). Phosphorylated p65 levels negatively correlated with menin expression (r2 = 0.42, P = 0.05). Tumor necrosis factor-α (TNFα) caused a significant increase in phosphorylated p65 levels (183 ± 13.8% of basal) while calcium sensing receptor (CaR) agonists exerted a significant inhibition (19.2 ± 3.3% of basal). Although TNFα was poorly effective in increasing cyclin D1 expression, NF-κB blockade by the specific inhibitor BAY11-7082 reduced FCS-stimulated cyclin D1 by about 60%. Finally, the inhibitory effects of CaR and BAY11-7082 on cyclin D1 expression were not additive – by blocking NF-κB CaR activation did not induce a further reduction in cyclin D1 levels. In conclusion, the study demonstrated that in parathyroid tumors: (1) p65 phosphorylation was dramatically increased by RET constitutive activation and was negatively correlated with menin expression, (2) p65 phosphorylation was increased and reduced by TNFα and CaR agonists respectively, and (3) blockade of the NF-κB pathway caused a significant decrease in cyclin D1 expression.
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Cheng, Shin-Ei, I.-Ta Lee, Chih-Chung Lin, Li-Der Hsiao та Chuen-Mao Yang. "Thrombin induces ICAM-1 expression in human lung epithelial cells via c-Src/PDGFR/PI3K/Akt-dependent NF-κB/p300 activation". Clinical Science 127, № 3 (3 квітня 2014): 171–83. http://dx.doi.org/10.1042/cs20130676.
Повний текст джерелаАнотація:
Up-regulation of ICAM-1 (intercellular adhesion molecule-1) is frequently implicated in lung inflammation and lung diseases, such as IPF (idiopathic pulmonary fibrosis). Thrombin has been shown to play a key role in inflammation via the induction of adhesion molecules, which then causes lung injury. However, the mechanisms underlying thrombin-induced ICAM-1 expression in HPAEpiCs (human pulmonary alveolar epithelial cells) remain unclear. In the present study, we have shown that thrombin induced ICAM-1 expression in HPAEpiCs. Pre-treatment with the inhibitor of thrombin [PPACK (D-Phe-Pro-Arg-chloromethyl ketone)], c-Src (PP1), PDGFR (platelet-derived growth factor receptor) (AG1296), PI3K (phosohinositide 3-kinase) (LY294002), NF-κB (nuclear factor κB) (Bay11-7082) or p300 (GR343) and transfection with siRNAs of c-Src, PDGFR, Akt, p65 and p300 markedly reduced thrombin-induced ICAM-1 expression and monocyte adherence to HPAEpiCs challenged with thrombin. In addition, we established that thrombin stimulated the phosphorylation of c-Src, PDGFR, Akt and p65, which were inhibited by pre-treatment with their respective inhibitors PP1, AG1296, LY294002 or Bay11-7082. In addition, thrombin also enhanced Akt and NF-κB translocation from the cytosol to the nucleus, which was reduced by PP1, AG1296 or LY294002. Thrombin induced NF-κB promoter activity and the formation of the p65–Akt–p300 complex, which were inhibited by AG1296, LY294002 or PP1. Finally, we have shown that thrombin stimulated in vivo binding of p300, Akt and p65 to the ICAM-1 promoter, which was reduced by AG1296, LY294002, SH-5 or PP1. These results show that thrombin induced ICAM-1 expression and monocyte adherence via a c-Src/PDGFR/PI3K/Akt/NF-κB-dependent pathway in HPAEpiCs. Increased understanding of the signalling mechanisms underlying ICAM-1 gene regulation will create opportunities for the development of anti-inflammatory therapeutic strategies.
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Zhang, Yanjun, Chunli Wang, Xiaona Li та Li Yang. "TGF-β1 and Mechanical-Stretch Induction of Lysyl-Oxidase and Matrix-Metalloproteinase Expression in Synovial Fibroblasts Requires NF-κB Pathways". Processes 10, № 8 (11 серпня 2022): 1574. http://dx.doi.org/10.3390/pr10081574.
Повний текст джерелаАнотація:
The imbalance in the expression of matrix metalloproteinases (MMPs) and lysyl oxidases (LOXs) in synovial fibroblasts (SFs) caused by mechanical injury and inflammatory response prevents injured anterior cruciate ligaments (ACLs) from self-healing. However, research on the effect of growth factors on SFs on regulating the microenvironment is limited. In this study, mechanical injury and exogenous transform growth factor-β1 (TGF-β1) were employed to mimic a joint-cavity microenvironment with ACL trauma. The function of the NF-κB transcription factor was further studied. The study found that the gene expression of LOXs (except LOXL-1), MMP-1, -2, and -3 in SFs was promoted by the combination of injurious mechanical stretching and TGF-β1 and that the upregulation of MMPs was higher than that of LOXs. In addition, MMP-2 activity induced by the combination of injurious stretch and TGF-β1 was inhibited by NF-κB inhibitors such as Bay11-7082 and Bay11-7085. The findings concluded that the synovium was an important regulator of the knee joint-cavity microenvironment after ACL injury and that the NF-κB pathway mediated the regulation of MMP-2 in SFs via mechanical factors and TGF-β1.
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Zheng, Qiang, Hang Zhao, Dong Jia, Xu Han, Zhenning Liu, and Min Zhao. "Overexpression of TOLLIP Protects against Acute Kidney Injury after Paraquat Intoxication through Inhibiting NLRP3 Inflammasome Activation Modulated by Toll-Like Receptor 2/4 Signaling." Mediators of Inflammation 2021 (July 14, 2021): 1–14. http://dx.doi.org/10.1155/2021/5571272.
Повний текст джерелаАнотація:
Paraquat (PQ) can cause multiorgan failure including acute kidney injury (AKI). Our prior study showed that Toll-interacting protein (TOLLIP) protected against PQ-induced acute lung injury. However, the role of TOLLIP in PQ-induced AKI remains undefined. This study was aimed at understanding the role and mechanism of TOLLIP in AKI. Six-eight-week-old male Wistar rats were intraperitoneally injected with 25 mg/kg PQ to induce AKI for 24 h in vivo. HK-2 cells were treated with 300 μM PQ for 24 h to induce cellular injury in vitro or 300 μM PQ and 5 μM nuclear factor-κB (NF-κB) inhibitor BAY11-7082 for 24 h. Rats were infected with adenovirus carrying TOLLIP shRNA via tail vein injection and HK-2 cells with adenovirus carrying TOLLIP shRNA or TOLLIP 48 h before PQ exposure. Results showed that TOLLIP and Toll-like receptor 2/4 (TLR2/4) expressions were boosted in the kidney after PQ intoxication. The toxic effect of PQ on the kidney and HK-2 cells was exacerbated by TOLLIP knockdown, as evidenced by aggravated glomerulus and tubule injury, inflammatory infiltration, and cell apoptosis in the kidney and increased loss of cell viability and apoptotic cells in HK-2 cells. TOLLIP knockdown also enhanced PQ-induced NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation in vivo and in vitro and TLR2/4-NF-κB signaling in vitro, reflected by increased contents of proinflammatory cytokines and expressions of NLRP3 inflammasome-related proteins in the kidney and HK-2 cells and expressions of TLR2, TLR4, and nuclear NF-κB p65 in HK-2 cells. However, TOLLIP overexpression inhibited PQ-induced loss of cell viability, cell apoptosis, NLRP3 inflammasome activation, and TLR2/4-NF-κB signaling in vitro. Additionally, BAY11-7082 abolished TOLLIP knockdown-induced NLRP3 inflammasome activation in vitro, indicating that TOLLIP protected against NLRP3 inflammasome activation in PQ-induced AKI through inhibiting TLR2/4-NF-κB signaling. This study highlights the importance of TOLLIP in AKI after PQ intoxication.
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Zhu, B., Z. Liu, P. Wang, C. Wu та H. Xu. "A Nuclear Factor-κB Inhibitor BAY11-7082 Inhibits Interactions Between Human Endothelial Cells, T Cells, and Monocytes". Transplantation Proceedings 40, № 8 (жовтень 2008): 2724–28. http://dx.doi.org/10.1016/j.transproceed.2008.07.129.
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Eichsteininger, Julia, Kerstin Kirisits, Claudia Smöch, Christa Stadlbauer, Chi Huu Nguyen, Walter Jäger, Ali Özmen, Gerhard Ecker, Georg Krupitza, and Liselotte Krenn. "Structural Insight into the In Vitro Anti-Intravasative Properties of Flavonoids." Scientia Pharmaceutica 87, no. 3 (September 3, 2019): 23. http://dx.doi.org/10.3390/scipharm87030023.
Повний текст джерелаАнотація:
We investigated the effect of 21 flavonoids in a three-dimensional in vitro system for their ability to inhibit gap formation by MCF-7 breast cancer spheroids in monolayers of lymphendothelial cells. Different representatives of the classes of flavones, flavonols, and flavanones were tested in the circular chemorepellent-induced defects (CCID)-assay. Bay11-7082, a known inhibitor of CCID formation served as the positive control. This study provides the first comparison of the potential of flavonoids to suppress features influencing the intravasation of MCF-7 breast cancer cells aggregates through the lymph endothelial barrier. The most significant effects were seen after incubation with the flavones luteolin, chrysin, and apigenin. Additional hydroxylation or methoxylation in positions 6 or 8, as expected, resulted in decreased activity. The tested flavanones remained without or low efficacy.
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Qiu, Zhen, Yuhong He, Hao Ming, Shaoqing Lei, Yan Leng, and Zhong-yuan Xia. "Lipopolysaccharide (LPS) Aggravates High Glucose- and Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes." Journal of Diabetes Research 2019 (February 17, 2019): 1–12. http://dx.doi.org/10.1155/2019/8151836.
Повний текст джерелаАнотація:
Diabetes aggravates myocardial ischemia-reperfusion (I/R) injury because of the combination effects of changes in glucose and lipid energy metabolism, oxidative stress, and systemic inflammatory response. Studies have indicated that myocardial I/R may coincide and interact with sepsis and inflammation. However, the role of LPS in hypoxia/reoxygenation (H/R) injury in cardiomyocytes under high glucose conditions is still unclear. Our objective was to examine whether lipopolysaccharide (LPS) could aggravate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by upregulating ROS production to activate NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. H9C2 cardiomyocytes were exposed to HG (30 mM) condition with or without LPS, along with caspase-1 inhibitor (Ac-YVAD-CMK), inflammasome inhibitor (BAY11-7082), ROS scavenger N-acetylcysteine (NAC), or not for 24 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). The cell viability, lactate dehydrogenase (LDH) release, caspase-1 activity, and intracellular ROS production were detected by using assay kits. The incidence of pyroptosis was detected by calcein-AM/propidium iodide (PI) double staining kit. The concentrations of IL-1β and IL-18 in the supernatants were assessed by ELISA. The mRNA levels of NLRP3, ASC, and caspase-1 were detected by qRT-PCR. The protein levels of NF-κB p65, NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18 were detected by western blot. The results indicated that pretreatment LPS with 1 μg/ml not 0.1 μg/ml could efficiently aggravate HG and H/R injury by activating NLRP3 inflammasome to mediate pyroptosis in H9C2 cells, as evidenced by increased LDH release and decreased cell viability in the cells, and increased expression of NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18. Meanwhile, Ac-YVAD-CMK, BAY11-7082, or NAC attenuated HG- and H/R-induced H9C2 cell injury with LPS stimulated by reversing the activation of NLRP3 inflammasome-mediated pyroptosis. In conclusion, LPS could increase the sensitivity of H9C2 cells to HG and H/R and aggravated HG- and H/R-induced H9C2 cell injury by promoting ROS production to induce NLRP3 inflammasome-mediated pyroptosis.
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Cheleschi, Sara, Nicola Giordano, Nila Volpi, Sara Tenti, Ines Gallo, Martina Di Meglio, Stefano Giannotti, and Antonella Fioravanti. "A Complex Relationship between Visfatin and Resistin and microRNA: An In Vitro Study on Human Chondrocyte Cultures." International Journal of Molecular Sciences 19, no. 12 (December 6, 2018): 3909. http://dx.doi.org/10.3390/ijms19123909.
Повний текст джерелаАнотація:
Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor (NF)-κB in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 μg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 μM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and NF-κB activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased miR-34a, miR-155, miR-181a, and miR-let7e, and reduced miR-140 and miR-146a gene expression in OA chondrocytes. MMP-1, MMP-13, and Col2a1 were significantly modulated by treatment of OA chondrocytes with adipokines. Visfatin and resistin significantly increased NF-κB activation, while the co-treatment with BAY11-7082 did not change MMPs or Col2a1 levels beyond that caused by single treatment. Visfatin and resistin regulate the expression levels of some miRNA involved in OA pathogenesis and exert catabolic functions in chondrocytes via the NF-κB pathway. These data confirm the complex relationship between adipokines and miRNA.
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Hu, Shuiqing, Qingqiong Luo, Biyun Cun, Dan Hu, Shengfang Ge, Xianqun Fan та Fuxiang Chen. "The Pharmacological NF-κB Inhibitor BAY11-7082 Induces Cell Apoptosis and Inhibits the Migration of Human Uveal Melanoma Cells". International Journal of Molecular Sciences 13, № 12 (23 листопада 2012): 15653–67. http://dx.doi.org/10.3390/ijms131215653.
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Xu, Chunming, Yanjun Zhang, Linawati Sutrisno, Li Yang, Rongfu Chen та K. L. Paul Sung. "Bay11-7082 facilitates wound healing by antagonizing mechanical injury- and TNF-α-induced expression of MMPs in posterior cruciate ligament". Connective Tissue Research 60, № 4 (29 жовтня 2018): 311–22. http://dx.doi.org/10.1080/03008207.2018.1512978.
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Wang, Weili, Zhaoyuan Zhang, Xingyi Kuang та Jishi Wang. "LSD1 Inhibitor 4SC-202 Inducing Apoptosis in Myelodysplastic Syndrome Cells Via NF-κb-HO-1 Pathway". Blood 134, Supplement_1 (13 листопада 2019): 5415. http://dx.doi.org/10.1182/blood-2019-130486.
Повний текст джерелаАнотація:
Aims: Human histone lysine-specific demethylase 1(LSD1) inhibit gene transcription and thereby block myeloid differentiation, apoptosis and cell cycle in AML. 4SC-202, a novel inhibitor of LSD1, is potential therapeutic agent for treating Myelodysplastic syndrome, while its mechanism of action remains unclear. M ainly method : In the study, LSD1 and HO-1 gene expression were detected in MDS/AML patients. After MDS cell line SKM-1 was treated with 4SC-202, cell viability, apoptosis and cell cycle were detected by CCK-8 or FACS. Lastly, western blotting analyzed that the agent caused the change of the related cellular function protein in SKM-1 cells. K ey findings: We found that LSD1 and HO-1 were overexpression in MDS/AML patients. LSD1 inhibitor 4SC-202 inhibited cell viability. The agent induced apoptosis by up-regulated BAX and cleaved caspase3/9 as well as down-regulated BCL-2, arrested cell cycle in the G2/M phase by down-regulated CDK1 and up-regulated p21, as well as inhibited activation of the NF-κB pathway and decreased HO-1. LSD1 and HO-1 expression were decreased after exposure with the NF-κB inhibitor OBY11-7082. Silencing LSD1 by LSD1 siRNA hardly caused apoptosis in SKM-1 cells, while the combination of Bay11-7082 and silencing LSD1 significantly decreased LSD1 and HO-1 expression and further increased apoptosis. While up-regulated HO-1 significantly limited the 4SC-202-induced down-regulation of BCL-2, up-regulation of cleaved caspase 3/9 and suppressed activation of NF-κB pathway as well as thereby attenuated the agent efficacy. S ignificant : In conclusion, LSD1 inhibitor 4SC-202 induced apoptosis through the NF-κB-mediated HO-1 pathway. LSD1 might be a potential target for the treatment of MDS. Disclosures No relevant conflicts of interest to declare.
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Zhang, Xiao, Keqin Yan, Lin Deng, Jing Liang, Haiyan Liang, Dingqing Feng та Bin Ling. "Cyclooxygenase 2 Promotes Proliferation and Invasion in Ovarian Cancer Cells via the PGE2/NF-κB Pathway". Cell Transplantation 28, № 1_suppl (грудень 2019): 1S—13S. http://dx.doi.org/10.1177/0963689719890597.
Повний текст джерелаАнотація:
Ovarian cancer is the leading cause of death among gynecological malignancies. Cyclooxygenase 2 is widely expressed in various cancer cells and participates in the occurrence and development of tumors by regulating a variety of downstream signaling pathways. However, the function and molecular mechanisms of cyclooxygenase 2 remain unclear in ovarian cancer. Here, we demonstrated that cyclooxygenase 2 was highly expressed in ovarian cancer and the expression level was highly correlated with ovarian tumor grades. Further, ovarian cancer cells with high expression of cyclooxygenase 2 exhibit enhanced proliferation and invasion abilities. Specifically, cyclooxygenase 2 promoted the release of prostaglandin E2 upregulated the phosphorylation levels of phospho-nuclear factor-kappa B p65. Celecoxib, AH6809, and BAY11-7082 all can inhibit the promoting effect of cyclooxygenase 2 on SKOV3 and OVCAR3 cell proliferation and invasion. Besides, celecoxib inhibited SKOV3 cell growth in the xenograft tumor model. These data suggest that high expression of cyclooxygenase 2 promotes the proliferation and invasion of ovarian cancer cells through the prostaglandin E2/nuclear factor-kappa B signaling pathway. Cyclooxygenase 2 may be a potential therapeutic target for the treatment of ovarian cancer.
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Viola, K., S. Kopf, N. Huttary, C. Vonach, N. Kretschy, M. Teichmann, B. Giessrigl, et al. "Bay11-7082 inhibits the disintegration of the lymphendothelial barrier triggered by MCF-7 breast cancer spheroids; the role of ICAM-1 and adhesion." British Journal of Cancer 108, no. 3 (October 23, 2012): 564–69. http://dx.doi.org/10.1038/bjc.2012.485.
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Yang, Hui, Wei Sun, Yan-nan Fan, Shu-yi Li, Ji-qiao Yuan, Zi-qian Zhang, Xu-yu Li, Ming-bao Lin, and Qi Hou. "Perilla Leaf Extract Attenuates Asthma Airway Inflammation by Blocking the Syk Pathway." Mediators of Inflammation 2021 (May 10, 2021): 1–14. http://dx.doi.org/10.1155/2021/6611219.
Повний текст джерелаАнотація:
Perilla frutescens (L.) Britton is a classic herbal plant used widely against asthma in China. But its mechanism of beneficial effect remains undermined. In the study, the antiallergic asthma effects of Perilla leaf extract (PLE) were investigated, and the underlying mechanism was also explored. Results showed that PLE treatment significantly attenuated airway inflammation in OVA-induced asthma mice, by ameliorating lung pathological changes, inhibiting recruitment of inflammatory cells in lung tissues and bronchoalveolar lavage fluid (BALF), decreasing the production of inflammatory cytokines in the BALF, and reducing the level of immunoglobulin in serum. PLE treatment suppressed inflammatory response in antigen-induced rat basophilic leukemia 2H3 (RBL-2H3) cells as well as in OVA-induced human peripheral blood mononuclear cells (PBMCs). Furthermore, PLE markedly inhibited the expression and phosphorylation of Syk, NF-κB, PKC, and cPLA2 both in vivo and in vitro. By cotreating with inhibitors (BAY61-3606, Rottlerin, BAY11-7082, and arachidonyl trifluoromethyl ketone) in vitro, results revealed that PLE’s antiallergic inflammatory effects were associated with the inhibition of Syk and its downstream signals NF-κB, PKC, and cPLA2. Collectively, the present results suggested that PLE could attenuate allergic inflammation, and its mechanism might be partly mediated through inhibiting the Syk pathway.
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Chen, Zixi, Yali Shan, Xingji You, Hang Gu, Chen Xu, Jing Long, and Xin Ni. "NLRP3 inflammasome is involved in uterine activation for labor at term and preterm." Reproduction 162, no. 6 (December 1, 2021): 449–60. http://dx.doi.org/10.1530/rep-21-0047.
Повний текст джерелаАнотація:
The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases. We sought to investigate the role of NLRP3 inflammasome in uterine activation for labor at term and preterm. We found that NLRP3 inflammasome was activated in the myometrium tissues obtained from the pregnant women undergoing labor at term (TL) compared with those not undergoing labor (TNL) at term. NLRP3 inflammasome was also activated in amnion and chorion-deciduas in TL and preterm labor (PTL) groups. In the mouse model, uterine NLRP3 inflammasome and nuclear factor kappaB (NF-κB) were activated toward term and during labor. Treatment of pregnant mice with lipopolysaccharide (LPS) and RU38486 induced preterm birth (PTB) and also promoted uterine NLRP3 inflammasome and NF-κB activation. Treatment of pregnant mice with NLRP3 inflammasome inhibitor BAY11-7082 and MCC950 delayed the onset of labor and suppressed NLRP3 inflammasome and NF-κB activation in uterus. MCC950 postponed labor onset of the mice with LPS and RU38486 treatment and inhibited NLRP3 inflammasome activation in uterus. Our data provide the evidence that NLRP3 inflammasome is involved in uterine activation for labor onset in term and PTB in humans and mouse model.
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Li, Weiping, Hongwei Li та Fusheng Gu. "CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells". Mediators of Inflammation 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/697832.
Повний текст джерелаАнотація:
Objective. The effects of C-reactive protein (CRP) and tumor necrosis factor-α(TNF-α) on pregnancy-associated plasma protein-A (PAPP-A) expression in human peripheral blood mononuclear cells (PBMCs) require further investigation.Methods. The PAPP-A levels in culture supernatants, PAPP-A mRNA expression, and cellular PAPP-A expression were measured in human PBMCs isolated from fresh blood donations provided by 6 healthy volunteers (4 donations per volunteer). Analyses were conducted by ultrasensitive ELISA, western blotting, and RT-PCR following stimulation with CRP or TNF-αcytokines.Results. PAPP-A mRNA and protein levels after CRP stimulation peaked at 24 hours, whereas peak PAPP-A mRNA and protein levels were achieved after TNF-αstimulation at only 2 and 8 hours, respectively. These findings indicate the dose-dependent effect of CRP and TNF-αstimulation. Actinomycin D treatment completely prevented CRP and TNF-αinduction of PAPP-A mRNA and protein expression. Additionally, nuclear factor- (NF-)κB inhibitor (BAY11-7082) potently inhibited both CRP and TNF-αstimulated PAPP-A mRNA and protein expression.Conclusions. Human PBMCs are capable of expressing PAPP-Ain vitro, expression that may be regulated by CRP and TNF-αthrough the NF-κB pathway. This mechanism may play a significant role in the observed increase of serum PAPP-A levels in acute coronary syndrome (ACS).
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Han, Shichao, Weixia Cai, Xuekang Yang, Yanhui Jia, Zhao Zheng, Hongtao Wang, Jun Li, et al. "ROS-Mediated NLRP3 Inflammasome Activity Is Essential for Burn-Induced Acute Lung Injury." Mediators of Inflammation 2015 (2015): 1–16. http://dx.doi.org/10.1155/2015/720457.
Повний текст джерелаАнотація:
The NLRP3 inflammasome is necessary for initiating acute sterile inflammation. However, its role in the pathogenesis of burn-induced acute lung injury (ALI) is unknown. This study aimed to determine the role of the NLRP3 inflammasome and the signaling pathways involved in burn-induced ALI. We observed that the rat lungs exhibited enhanced inflammasome activity after burn, as evidenced by increased levels of NLRP3 expression and Caspase-1 activity and augmented inflammatory cytokines. Inhibition of NLRP3 inflammasome by BAY11-7082 attenuated burn-induced ALI, as demonstrated by the concomitant remission of histopathologic changes and the reduction of myeloperoxidase(MPO) activity, inflammatory cytokines in rat lung tissue, and protein concentrations in the bronchoalveolar lavage fluid (BALF). In thein vitroexperiments, we used AMs (alveolar macrophages) challenged with burn serum to mimic the postburn microenvironment and noted that the serum significantly upregulated NLRP3 inflammasome signaling and reactive oxygen species (ROS) production. The use of ROS scavenger N-acetylcysteine (NAC) partially reversed NLRP3 inflammasome activity in cells exposed to burn serum. These results indicate that the NLRP3 inflammasome plays an essential role in burn-induced ALI and that burn-induced NLRP3 inflammasome activity is a partly ROS-dependent process. Targeting this axis may represent a promising therapeutic strategy for the treatment of burn-induced ALI.
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Lin, Yuanqiang, Qingjie Ma, Lin Li та Hui Wang. "The CXCL12–CXCR4 axis promotes migration, invasiveness, and EMT in human papillary thyroid carcinoma B-CPAP cells via NF-κB signaling". Biochemistry and Cell Biology 96, № 5 (жовтень 2018): 619–26. http://dx.doi.org/10.1139/bcb-2017-0074.
Повний текст джерелаАнотація:
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy involving local and distant metastasis. It is known that CXC chemokine ligand 12 (CXCL12) interacts specifically with CXC chemokine receptor 4 (CXCR4) to guide the migration of PTC cells. However, the signaling pathway downstream of the CXCL12–CXCR4 axis in PTC is not fully understood. In the present study, high expression of CXCR4 was detected in 38 out of 82 specimens of PTC, and the expression level of CXCR4 significantly correlated with the stage of PTC. Additionally, the roles of the CXCL12–CXCR4 axis in the migration, invasion, and epithelial–mesenchymal transition (EMT) of B-CPAP cells were investigated in vitro. The motility and invasiveness were significantly enhanced in CXCR4-overexpressing B-CPAP cells with CXCL12 treatment. Moreover, the CXCL12–CXCR4 axis promoted the EMT process, as evidenced by a decreased level of E-cadherin and increased expressions of N-cadherin and vimentin. Furthermore, the CXCL12–CXCR4 axis activated the nuclear factor kappa-B (NF-κB) signaling pathway, whereas BAY11-7082, an IκB phosphorylation inhibitor, counteracted CXCL12–CXCR4-induced migration, invasion, and EMT processes in B-CPAP cells. In conclusion, the CXCL12–CXCR4 axis promotes the migration, invasion, and EMT processes in B-CPAP cells, at least partly, by activating the NF-κB signaling pathway.
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Kang, Byungjin, Joo-Hoo Park та Heung-Man Lee. "Histamine Induced Production of Chemokine CXCL8 Through H1R/PLC and NF-κB Signaling Pathways in Nasal Fibroblasts". Journal of Rhinology 27, № 2 (30 листопада 2020): 95–101. http://dx.doi.org/10.18787/jr.2019.00302.
Повний текст джерелаАнотація:
Background and Objectives: Histamine has been suggested to play an important role during allergic and inflammatory reactions, affecting allergic rhinitis and chronic rhinosinusitis. CXCL8 is a pro-inflammatory chemokine and a critical factor that causes many airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.Materials and Method: Histamine cytotoxicity was measured by MTT assay. Real-time polymerase chain reaction was used to identify histamine type 1 receptor in nasal fibroblasts. The fibroblasts were then treated with histamine with or without a histamine type 1 receptor antagonist and the CXCL8 protein was assessed using an enzyme-linked immunosorbent assay (ELISA). The downstream signaling molecules, including phospholipase C and phospho-p50, were evaluated by western blot and immunofluorescent staining.Results: Histamine had no significant cytotoxic effect until the concentration reached 1,000 μM. Histamine type 1 receptor mRNA was expressed in nasal fibroblasts. CXCL8 protein expression level was significantly increased following histamine stimulation. However, the expression level of CXCL8 decreased when phospholipase C was inhibited by U73122. Histamine increased phospho-p50 expression as seen in western blot results. The BAY11-7082, NF-κB inhibitor significantly reduced CXCL8 production in histamine-stimulated nasal fibroblasts.Conclusion: Histamine can induce the production of NF-κB controlled-chemokine CXCL8 by nasal fibroblasts, which supports a role for histamine in upper airway inflammatory diseases.
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Morotti, Alessandro, Daniela Cilloni, Riccardo Taulli, Francesca Arruga, Renata Catalano, Francesca Messa, Ilaria Defilippi, et al. "Overexpression of the p65 Subunit of NF-kB and IkB Mediated Nuclear Sequestration of p53 as Common Events in Philadelphia Positive and Negative Chronic Myeloid Leukemia." Blood 106, no. 11 (November 16, 2005): 2871. http://dx.doi.org/10.1182/blood.v106.11.2871.2871.
Повний текст джерелаАнотація:
Abstract Introduction. Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia translocation. Rare patients with a clinical presentation of CML are negative for the Ph chromosome. The pathogenesis of Ph negative CML is still unknown. Different reports have demonstrated that the transcription factor NF-kappaB is essential for Bcr-Abl mediated transformation. NF-kappaB is composed of two subunits (mainly p65 and p50) which are retained into the cytoplasm by the inhibitory protein IkappaB-alpha. Different stimuli trigger IkappaB degradation and nuclear translocation of NF-kappaB, where it mediates the transcription of different genes involved in cellular proliferation, transformation and resistance to apoptosis. Aim of the work. We have evaluated the role of NF-kappaB in primary chronic myeloid leukemia samples both positive and negative for the Philadelphia chromosome. Methods. Bone marrow samples of 10 chronic myeloproliferative disorders (6 Ph positive and 4 Ph negative CML), 1 CML blast phase, 2 Acute Myeloid Leukemia and 3 healthy donor have been collected at diagnosis. Each sample has been lysed to obtain cytosolic and nuclear extracts. Western blot have been performed to evaluate the expression of p65 and the regulatory protein IkappaB-alpha. DNA binding activity of NF-kappaB has been measured with an ELISA method (TransAM). To inhibit NF-kB, primary cells have been incubated with 1 microM MG-132, 90 microM Resveratrol and 5 microM Bay11-7082 or have been infected with a lentivirus construct containing dsRNA directed against the p65 subunit of NF-kB and a lentivirus expressing a mutated IKB which retains NF-kB inactive in the cytoplasm. Results. Ph+ and Ph- CML samples express both in the cytosol and in the nucleus higher levels of p65 respect to normal peripheral blood and normal bone marrow samples. In normal samples IkB-alpha is detectable only in the cytosol while in Ph+ and Ph- CML samples it is predominately expressed in the nucleus. DNA binding activity of NF-kappaB is not particularly increased in CML respect to normal bone marrow samples. Only CML blast phase and Acute Myeloid Leukemia show markedly increased DNA binding activity of NF-kappaB. Immunoprecipitates of nuclear and cytosolic IkappaB-alpha have been performed. The pro-apoptotic p53 co-immunoprecipitates with IkappaB-alpha. Treatment with NF-kappaB inhibitors MG-132, Resveratrol and Bay11-7082 disrupts p53-IkBalpha dimer rendering cells susceptible to the apoptotic stimulation induced by Doxorubicine. To confirm these data, primary CML samples have also been infected with a lentivirus construct containing dsRNA directed against p65 and a lentivirus expressing a mutated IKB which retains NF-kB inactive in the cytoplasm. In both cases cells becomes more sensitive to Doxorubicin-induced apoptosis, due to disruption of IkB - p53 dimer. Conclusion. Nuclear and cytosolic IkappaB-alpha mediated p53 sequestration is a common event in both Ph+ and Ph- CML, which may contribute to the pathogenesis of this disorder due to impairment of p53 pro-apoptotic functions. NF-kB inhibition may represent a powerful strategy to render CML cells more susceptible to apotosis.
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Zhang, Qi, Zujie Mao та Juan Sun. "NF-κB inhibitor, BAY11-7082, suppresses M2 tumor-associated macrophage induced EMT potential via miR-30a/NF-κB/Snail signaling in bladder cancer cells". Gene 710 (серпень 2019): 91–97. http://dx.doi.org/10.1016/j.gene.2019.04.039.
Повний текст джерела
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Yao, Feiqun, та Qian Zhu. "α-Cyperone Protects Cardiomyocytes against Oxygen-Glucose Deprivation-Induced Inflammation and Oxidative Stress by Akt/FOXO3a/NF-κB Pathway". Disease Markers 2022 (29 серпня 2022): 1–14. http://dx.doi.org/10.1155/2022/8205707.
Повний текст джерелаАнотація:
Objective. This study is aimed at investigating the mechanism of α-cyperone in oxygen and glucose deprivation- (OGD-) induced myocardial injury. Methods. Cardiomyocytes were exposed to OGD and then treated with α-cyperone. The cell counting kit-8 (CCK-8) assay and flow cytometry were performed to determine cell proliferation and apoptosis, respectively. The expression of inflammatory factors was monitored by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The profiles of apoptosis-related proteins, inflammatory proteins, and the Akt/FOXO3a/NF-κB pathway were determined by western blot. The phosphorylation of Akt, FOXO3a, and NF-κB was determined by immunofluorescence assay. The superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content were gauged by the colorimetric method, and the reactive oxygen species (ROS) content was measured. Results. α-Cyperone hindered OGD-induced inflammation, oxidative stress, and apoptosis in cardiomyocytes. OGD activated the FOXO3a/NF-κB pathway and hampered the Akt phosphorylation. α-cyperone reversed OGD-mediated FOXO3a/NF-κB pathway activation. Treatment with MK-2206 abated the protective effect of α-cyperone against OGD-induced myocardial injury. The addition of α-cyperone to cardiomyocytes following Bay11-7082 treatment had no conspicuous effect on the viability and apoptosis. Conclusions. α-Cyperone protected cardiomyocytes against OGD-induced inflammation and oxidative stress via the Akt/FOXO3a/NF-κB axis.
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Xu, Zhaohui, Ruitao Liu, Ling Huang, Yuxin Xu, Mingmin Su, Jiayu Chen, Lanlan Geng, Wanfu Xu та Sitang Gong. "CD147 Aggravated Inflammatory Bowel Disease by Triggering NF-κB-Mediated Pyroptosis". BioMed Research International 2020 (2 липня 2020): 1–8. http://dx.doi.org/10.1155/2020/5341247.
Повний текст джерелаАнотація:
Background. Pyroptosis, a novel form of inflammatory programmed cell death, was recently found to be a cause of mucosal barrier defect. In our pervious study, CD147 expression was documented to increase in intestinal tissue of inflammatory bowel disease (IBD). Objective. The aim of this study was to determine the function of serum CD147 in pyroptosis. Methods. The study group consisted of 96 cases. The centration of CD147, IL-1β, and IL-18 levels in serum was assessed by ELISA. Real-time PCR and WB were performed to analyze the effect of CD147 on pyroptosis. Results. In this study, our results showed that CD147 induced cell pyroptosis in intestinal epithelial cells (IECs) by enhancement of IL-1β and IL-18 expression and secretion in IECs, which is attributed to activation of inflammasomes, including caspase-1 and GSDMD as well as GSDME, leading to aggregate inflammatory reaction. Mechanically, CD147 promoted phosphorylation of NF-κB p65 in IECs, while inhibition of NF-κB activity by the NF-κB inhibitor BAY11-7082 reversed the effect of CD147 on IL-1β and IL-18 secretion. Most importantly, serum CD147 level is slightly clinically correlated with IL-1β, but not IL-18 level. Conclusion. These findings revealed a critical role of CD147 in the patients with IBD, suggesting that blockade of CD147 may be a novel therapeutic strategy for the patients with IBD.
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Zeuner, Marie-Theres, Thomas Vallance, Sakthivel Vaiyapuri, Graeme S. Cottrell та Darius Widera. "Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation". Mediators of Inflammation 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/6209865.
Повний текст джерелаАнотація:
Aberrant activation of the transcription factor NF-κB, as well as uncontrolled inflammation, has been linked to autoimmune diseases, development and progression of cancer, and neurological disorders like Alzheimer’s disease. Reporter cell lines are a valuable state-of-the art tool for comparative analysis of in vitro drug screening. However, a reporter cell line for the investigation of NF-κB-driven neuroinflammation has not been available. Thus, we developed a stable neural NF-κB-reporter cell line to assess the potency of proinflammatory molecules and peptides, as well as anti-inflammatory pharmaceuticals. We used lentivirus to transduce the glioma cell line U251-MG with a tandem NF-κB reporter construct containing GFP and firefly luciferase allowing an assessment of NF-κB activity via fluorescence microscopy, flow cytometry, and luminometry. We observed a robust activation of NF-κB after exposure of the reporter cell line to tumour necrosis factor alpha (TNFα) and amyloid-β peptide [1-42] as well as to LPS derived from Salmonella minnesota and Escherichia coli. Finally, we demonstrate that the U251-NF-κB-GFP-Luc reporter cells can be used for assessing the anti-inflammatory potential of pharmaceutical compounds using Bay11-7082 and IMD0354. In summary, our newly generated cell line is a robust and cost-efficient tool to study pro- and anti-inflammatory potential of drugs and biologics in neural cells.
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Chiadak, Jeanne Durendale, Tatjana Arsenijevic, Kevin Verstrepen, Françoise Gregoire, Nargis Bolaky, Valérie Delforge, Véronique Flamand, Jason Perret та Christine Delporte. "Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB". Mediators of Inflammation 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/1431789.
Повний текст джерелаАнотація:
In an obese state, Toll-like receptor-4 (TLR-4) upregulates proinflammatory adipokines secretion including monocyte chemotactic protein-1 (MCP-1) in adipose tissue. In contrast, G-protein coupled receptor 120 (GPR120) mediates antiobesity effects. The aim of this study was to determine the signaling pathway by which Forskolin (FK), a cyclic adenosine monophosphate- (cAMP-) promoting agent causing positive changes in body composition in overweight and obese adult men, affects MCP-1 and GPR120 expression during an inflammatory response induced by lipopolysaccharide (LPS) in adipocytes, such as in an obese state. 3T3-L1 cells differentiated into adipocytes (DC) were stimulated with LPS in the absence or presence of FK and inhibitors of TLR-4 and inhibitor of kappa B (IκBα). In DC, LPS increased MCP-1, TLR-4, and nuclear factor-κB1 (NFκB1) mRNA levels, whereas it decreased GPR120 mRNA levels. In DC, FK inhibited the LPS-induced increase in MCP-1, TLR-4, and NFκB1 mRNA levels and the LPS-induced decrease in GPR120 mRNA. BAY11-7082 and CLI-095 abolished these LPS-induced effects. In conclusion, FK inhibits LPS-induced increase in MCP-1 mRNA levels and decrease in GPR120 mRNA levels in adipocytes and may be a potential treatment for inflammation in obesity. Furthermore, TLR-4-induced activation of NFκB may be involved in the LPS-induced regulation of these genes.
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Hosono, Naoko, Shinji Kishi, Sumiko Iho, Yoshimasa Urasaki, Akira Yoshida, Hisanori Kurooka, Yoshifumi Yokota та Takanori Ueda. "Unique Resistance Mechanism to Dexamethasone by Glutathione S-Transferase M1 Involving p38 MAPK and NF-κB Pathways, Possible Prognostic Role for Childhood ALL." Blood 110, № 11 (16 листопада 2007): 2375. http://dx.doi.org/10.1182/blood.v110.11.2375.2375.
Повний текст джерелаАнотація:
Abstract Glutathione S-transferases (GSTs) are known as detoxification enzymes that catalyse the conjugation of glutathione to anticancer drugs. In addition to this activity, GSTM1, an isotype of the Mu class GSTs, has been suggested to act as a negative regulator of mitogen-activated protein kinase (MAPK) activation. About 40–60% of the population has a deficit in GSTM1 enzyme activity, and the patients possessing GSTM1 have been reported to have a greater risk of relapse in childhood acute lymphoblastic leukemia (ALL). However, the reasons for poor prognosis remain unclear. To establish our hypothesis that GSTM1-induced drug resistance was involved, GSTM1 was transfected into GSTM1-negative CCRF-CEM cell lines (hereafter, the transfectant is denoted as CEM/M1) and the drug sensitivity was compared with that of control cells (CEM/mock). CEM/M1 showed decreased sensitivity to melphalan and carmustine (relative resistance vs. CEM/mock: 1.6 and 2.1, respectively; p<0.05), but not to daunorubicin, vincristine or etoposide. Notably, sensitivity to dexamethasone (DEX) decreased to a degree of up to 8-fold (IC50:1.76 μM in CEM/M1 and 0.22 μM in CEM/mock; p<0.01). Glutathione depletion by buthionine sulfoximine abrogated the resistance of CEM/M1 to alkylating agents, but not to DEX. These results suggest that a different mechanism is involved in the resistance to DEX. To clarify the GSTM1-related DEX resistance, proapoptotic pathway via p38 MAPK was evaluated. In CEM/M1, DEX-induced apoptosis was significantly inhibited (annexin V-positive at 72hr: 27% in CEM/M1 and 57% in CEM/mock; p<0.01). Silencing of GSTM1 by siRNA restored the DEX resistance, indicating that the anti-apoptosis was caused by the expression of GSTM1. After the treatment with DEX, phosphorylation of p38 was upregulated in CEM/mock, but not in CEM/M1; and the level of Bim mRNA was higher in CEM/mock than it was in CEM/M1. These findings indicate that the overexpression of GSTM1 down-regulates the proapoptotic pathway via p38 MAPK-Bim. However, treatment with a p38 MAPK-inhibitor (SB202194) decreased the DEX-induced apoptosis in both CEM/mock and CEM/M1. The involvement in DEX-resistance seems to be partial. To investigate other mechanisms, NF-κB pathway was evaluated. The basal activity of NF-κB p50 was significantly higher in CEM/M1 than it was in CEM/mock. Inhibition of IκBα phosphorylation by BAY11-7082 increased DEX sensitivity in either cells. Of considerable importance, however, is that the increase by BAY11-7082 was prominent in CEM/M1 and the relative resistance decreased from 8 to 2-fold. It appears that the anti-apoptotic NF-κB pathway is also involved in a resistance to DEX. In conclusion, the expression of GSTM1 in CCRF-CEM caused the resistance to alkylating agents due to its catalytic activity and to DEX by its anti-apoptotic function. The latter is the first report demonstrating the relationship between the expression of GSTM1 and DEX resistance. The determination of GSTM1 expression could be a useful tool for the individualization of optimize therapy for childhood ALL. (Supported by JSPS grant C19591102 and JRFCP grant)
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Hsu, Hui-Chi, Wen-Hui Tsai, and Yu-Chieh Lin. "CD14 Mediates Phagocytic Activity during the Granulocytic Differentiation Process in Acute Promyelocytic Leukemia Cells." Blood 124, no. 21 (December 6, 2014): 4955. http://dx.doi.org/10.1182/blood.v124.21.4955.4955.
Повний текст джерелаАнотація:
Abstract All-trans retinoic acid (ATRA) can induce acute promyelocytic leukemia (APL) cells differentiation into mature granulocytes. CD14 and Toll-like receptor 4 (TLR-4) play an important role in the phagocytic activity of macrophage, however, their role during granulopoiesis is still unclear. In this study, we determined the role of CD14/TLR-4 in the development of phagocytic activity in NB4 APL cells after induction into the process of granulocytic differentiation by ATRA. Flow cytometry analysis demonstrate that, during ATRA treatment for 6 days, the phagocytic activity of NB4 cells in engulfing either fluorescein-latex beads or idarubicin-induced apoptotic cells increased in a time-dependent manner, and the level of CD14 expression on NB4 cells was also significantly increased in a time dependent manner, though its level was only minimally expressed in ATRA-untreated NB4 cells. However, TLR-4 was constitutionally expressed in ATRA-untreated cells and its level did not changed significantly during the first 5 days of ATRA treatment. Further study demonstrates that the phagocytic activity of ATRA-NB4 cells was significantly inhibited by pre-treating cells with antibodies specific to either CD14 or TLR-4 before phagocytosis assay. In exploring the role of CD14/TLR4 associated signal transduction mediators, NF-κB and IRF-3, we further demonstrate that the phagocytic activity of ATRA-NB4 cells in engulfing beads was significantly inhibited when cells were pretreated with either a NF-κB inhibitor (BAY 11-7082) or an IRF-3 inhibitor (SP600125). However, this activity in engulfing apoptotic cells was only significantly inhibited by pretreatment with BAY11-7082, but not by pre-treatment with SP600125. Finally, our results indicate that the level of CD14(+) microparticles (MPs) released by ATRA-NB4 cells was significantly enhanced when those cells were induced into the process of apoptosis by pre-treatment with idarubicin. Moreover, by incubation with MPs derived from apoptotic ATRA-NB4 cells, the phagocytic activity of living ATRA-NB4 cells in engulfing apoptotic cells was significantly enhanced, and this phagocytic activity was also significantly inhibited by pre-treating MPs with antibody specific to CD14 before phagocytic assay. We conclude that CD14 contributes to the phagocytic activity of APL cells during the process of granulocytic differentiation. Disclosures No relevant conflicts of interest to declare.
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Xiao, Kan, Congcong Liu, Zhixiao Tu, Qiao Xu, Shaokui Chen, Yang Zhang, Xiuying Wang, Jing Zhang, Chien-An Andy Hu та Yulan Liu. "Activation of the NF-κB and MAPK Signaling Pathways Contributes to the Inflammatory Responses, but Not Cell Injury, in IPEC-1 Cells Challenged with Hydrogen Peroxide". Oxidative Medicine and Cellular Longevity 2020 (21 січня 2020): 1–14. http://dx.doi.org/10.1155/2020/5803639.
Повний текст джерелаАнотація:
Oxidative stress can lead to intestinal cell injury as well as the induction of inflammation. It is not clear whether inflammation is an important factor leading to cell injury caused by oxidative stress. The purpose of this study was to investigate the role of inflammation in intestinal injury caused by hydrogen peroxide (H2O2). Our results revealed that H2O2 stimulation significantly decreased the viability of intestinal porcine epithelial cells (IPEC-1), increased lactate dehydrogenase (LDH) activity, and disrupted the distribution of the tight junction protein claudin-1. H2O2 significantly increased the mRNA expression of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). H2O2 stimulation also led to increased phosphorylation of p38 and jun N-terminal kinase (JNK), and p65 NF-κB protein translocation into the nucleus of IPEC-1 cells. Cells treated with the NF-κB inhibitor (BAY11-7082), the p38 inhibitor (SB202190), or the JNK inhibitor (PD98059) significantly decreased mRNA and protein expression of IL-6, IL-8, and TNF-α. However, treatment with mitogen-activated protein kinase (MAPK) or NF-κB inhibitors did not prevent the damage effect on cell viability, LDH activity, or the distribution of claudin-1 in cells challenged with H2O2. In summary, our data demonstrate that activation of the NF-κB and MAPK signaling pathways can contribute to the inflammatory response, but not cell injury, in IPEC-1 cells challenged with H2O2.
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Jiang, Lei, Chan Xu, Yan Zhao, Qinghua Huang, Wufeng Yuan, Yan Wu, and Xianming Fei. "Papain ameliorates monocyte-platelet aggregate formation-mediated inflammatory responses in monocytes by upregulating miRNA-146a transcription." PLOS ONE 17, no. 11 (November 21, 2022): e0278059. http://dx.doi.org/10.1371/journal.pone.0278059.
Повний текст джерелаАнотація:
Background MicroRNA-146a (miRNA-146a) is a nuclear factor κB (NF-κB)-inducible and inflammation-sensitive miRNA, while papain elicits anti-inflammatory effects by inhibiting monocyte-platelet aggregate (MPA)-mediated NF-κB pathway activation in monocytes. This study aimed to demonstrate the underlying effects of papain on MPA formation-initiated miRNA-146a expression and subsequent action in monocytes. Methods THP-1 cells were exposed to papain, miRNA-146a mimic and inhibitor, NF-κB inhibitor (BAY11-7082), and platelets. Flow cytometry was used to measure the MPA formation-initiated monocyte activation. Levels of miRNA-146a, cyclooxygenase 2 (COX-2) mRNA and protein, and monocyte chemoattractant protein 1 (MCP-1) were analyzed in monocytes by RT-PCR, western blot, and ELISA. Results The NF-κB inhibitor and miRNA-146a mimics upregulated miRNA-146a expression but suppressed subsequent monocyte activation and expression of COX-2 and MCP-1. Following exposure to papain, the enhanced miRNA-146a transcription induced by MPA-formation was found along with significant inhibition of monocyte activation in a dose-dependent manner. However, the inhibitory tendency was significantly reversed by miRNA-146a inhibitors. Expression of COX-2 mRNA and protein, as well as MCP-1, was inhibited in monocytes by papain, whereas miRNA-146a inhibitors promoted COX-2 and MCP-1 expression. Conclusion Our findings suggest that papain can inhibit MPA formation-mediated expression of inflammatory mediators in activated monocytes by upregulating miRNA-146a transcription.
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Zhang, Yali, Yu Fu, Chenyang Zhang, Linying Jia, Nuo Yao, Yuhao Lin, Yue Dong, et al. "MED1 Deficiency in Macrophages Accelerates Intimal Hyperplasia via ROS Generation and Inflammation." Oxidative Medicine and Cellular Longevity 2021 (November 22, 2021): 1–19. http://dx.doi.org/10.1155/2021/3010577.
Повний текст джерелаАнотація:
Mediator complex subunit 1 (MED1) is a component of the mediator complex and functions as a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Previously, we showed that MED1 in macrophages has a protective effect on atherosclerosis; however, the effect of MED1 on intimal hyperplasia and mechanisms regulating proinflammatory cytokine production after macrophage MED1 deletion are still unknown. In this study, we report that MED1 macrophage-specific knockout (MED1ΔMac) mice showed aggravated neointimal hyperplasia, vascular smooth muscle cells (VSMCs), and macrophage accumulation in injured arteries. Moreover, MED1ΔMac mice showed increased proinflammatory cytokine production after an injury to the artery. After lipopolysaccharide (LPS) treatment, MED1ΔMac macrophages showed increased generation of reactive oxygen species (ROS) and reduced expression of peroxisome proliferative activated receptor gamma coactivator-1α (PGC1α) and antioxidant enzymes, including catalase and glutathione reductase. The overexpression of PGC1α attenuated the effects of MED1 deficiency in macrophages. In vitro, conditioned media from MED1ΔMac macrophages induced more proliferation and migration of VSMCs. To explore the potential mechanisms by which MED1 affects inflammation, macrophages were treated with BAY11-7082 before LPS treatment, and the results showed that MED1ΔMac macrophages exhibited increased expression of phosphorylated-p65 and phosphorylated signal transducer and activator of transcription 1 (p-STAT1) compared with the control macrophages, suggesting the enhanced activation of NF-κB and STAT1. In summary, these data showed that MED1 deficiency enhanced inflammation and the proliferation and migration of VSMCs in injured vascular tissue, which may result from the activation of NF-κB and STAT1 due to the accumulation of ROS.
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Olajide, Olumayokun A., Victoria U. Iwuanyanwu, Oyinkansola D. Adegbola, and Alaa A. Al-Hindawi. "SARS-CoV-2 Spike Glycoprotein S1 Induces Neuroinflammation in BV-2 Microglia." Molecular Neurobiology 59, no. 1 (October 28, 2021): 445–58. http://dx.doi.org/10.1007/s12035-021-02593-6.
Повний текст джерелаАнотація:
AbstractIn addition to respiratory complications produced by SARS‐CoV‐2, accumulating evidence suggests that some neurological symptoms are associated with the disease caused by this coronavirus. In this study, we investigated the effects of the SARS‐CoV‐2 spike protein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF-α, IL-6, IL-1β and iNOS/NO. S1 also increased protein levels of phospho-p65 and phospho-IκBα, as well as enhanced DNA binding and transcriptional activity of NF-κB. These effects of the protein were blocked in the presence of BAY11-7082 (1 µM). Exposure of S1 to BV-2 microglia also increased the protein levels of NLRP3 inflammasome and enhanced caspase-1 activity. Increased protein levels of p38 MAPK was observed in BV-2 microglia stimulated with the spike protein S1 (100 ng/ml), an action that was reduced in the presence of SKF 86,002 (1 µM). Results of immunofluorescence microscopy showed an increase in TLR4 protein expression in S1-stimulated BV-2 microglia. Furthermore, pharmacological inhibition with TAK 242 (1 µM) and transfection with TLR4 small interfering RNA resulted in significant reduction in TNF-α and IL-6 production in S1-stimulated BV-2 microglia. These results have provided the first evidence demonstrating S1-induced neuroinflammation in BV-2 microglia. We propose that induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-κB and p38 MAPK, possibly as a result of TLR4 activation. These results contribute to our understanding of some of the mechanisms involved in CNS pathologies of SARS-CoV-2.
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Hu, Wenjie, Lin Wen, Fang Cao та Yexin Wang. "Down-Regulation of Mir-107 Worsen Spatial Memory by Suppressing SYK Expression and Inactivating NF-ΚB Signaling Pathway". Current Alzheimer Research 16, № 2 (4 лютого 2019): 135–45. http://dx.doi.org/10.2174/1567205016666181212154347.
Повний текст джерелаАнотація:
Background: Alzheimer’s Disease (AD) is a chronic progressive neurodegenerative disorder in a central nervous system seen. Objective: We aimed to study the miR-107 in Alzheimer's Disease (AD) pathology through regulating SYK and NF-κB signaling pathway. </P><P> Method: Bioinformatics analysis was performed to screen NF-κB signaling pathway and differentially expressed genes. The target relationship between miR-107 and SYK was verified by dual luciferase assay. QRT-PCR and western blot analysis were used to verify the expression level of miR-107, SYK and NF- κB signaling pathway related proteins of hippocampus primary neurons. BAY61-3606 and BAY11-7082 were purchased for functional examination. Morris water maze tests were performed to access spatial memory of AD mice with SYK and NF-κB signaling pathway inhibition. Fluorescence microscope dyeing experiment investigated the neurons nuclear form and apoptosis. Results: MiR-107 was lowly expressed while SYK was highly expressed in Tg19959 mouse model. Luciferase Assay confirmed the target relationship in miR-107 and SYK. With the inhibition of miR-107, SYK was up-regulated and the increase of p-p65 and the decrease of p-IκB-α suggested that NF-κB signaling pathway was activated in vitro. Morris water maze test indicated that the spatial memory of Tg19959 mice was increased with the treatment. The result of DAPI staining indicated that the inhibition of SYK or NF-κB signaling pathway reduced the apoptosis of Tg19959 mice neuron cell. Conclusion: MiR-107 exerts its effects through suppression of the NF-κB signaling pathway and SYK, the inhibition of SYK and NF-κB signaling pathway can improve spatial memory and suppress cell apoptosis.
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Kumar, Naveen, Zhong-tao Xin, Yuhong Liang, Hinh Ly та Yuying Liang. "NF-κB Signaling Differentially Regulates Influenza Virus RNA Synthesis". Journal of Virology 82, № 20 (13 серпня 2008): 9880–89. http://dx.doi.org/10.1128/jvi.00909-08.
Повний текст джерелаАнотація:
ABSTRACT The NF-κB signaling pathway has previously been shown to be required for efficient influenza A virus replication, although the molecular mechanism is not well understood. In this study, we identified a specific step of the influenza virus life cycle that is influenced by NF-κB signaling by using two known NF-κB inhibitors and a variety of influenza virus-specific assays. The results of time course experiments suggest that the NF-κB inhibitors Bay11-7082 and ammonium pyrrolidinedithiocarbamate inhibited an early postentry step of viral infection, but they did not appear to affect the nucleocytoplasmic trafficking of the viral ribonucleoprotein complex. Instead, we found that the levels of influenza virus genomic RNA (vRNA), but not the corresponding cRNA or mRNA, were specifically reduced by the inhibitors in virus-infected cells, indicating that NF-κB signaling is intimately involved in the vRNA synthesis. Furthermore, we showed that the NF-κB inhibitors specifically diminished influenza virus RNA transcription from the cRNA promoter but not from the vRNA promoter in a reporter assay, a result which is consistent with data obtained from virus-infected cells. The overexpression of the p65 NF-κB molecule could not only eliminate the inhibition but also activate influenza virus RNA transcription from the cRNA promoter. Finally, using p65-specific small interfering RNA, we have shown that p65 knockdown reduced the levels of influenza virus replication and vRNA synthesis. In summary, we have provided evidence showing, for the first time, that the NF-κB host signaling pathway can differentially regulate influenza virus RNA synthesis, which may also offer some new perspectives into understanding the host regulation of RNA synthesis by other RNA viruses.