Добірка наукової літератури з теми "Jf799.5 .p65 2016"

The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats.

The study was carried out to define whether prednisolone-induced damage to hepatic cells is accompanied by excessive nitric oxide (NO) levels associated with nuclear factor kappa B (NF-κB)/inducible NO synthase (iNOS) activation and evaluate the efficacy of the treatment with vitamin D3. Histopathological examination, activities of liver transaminases (alanine aminotransferase and aspartate aminotransferase), and cell death assays consistently showed that prednisolone (5 mg/kg body weight, 30 days) induces chronic liver injury in female Wistar rats. Specifically, increased hepatocellular necrosis and caspase-3-dependent apoptosis were observed. Prednisolone enhanced iNOS protein expression, NO generation, and tyrosine nitration in liver cells. Despite unchanged hepatic level of the NF-κB/p65 protein, prednisolone increased inhibitory κB-α (IκB-α) degradation, nuclear translocation, and phosphorylation of NF-κB/p65 at Ser311, indicating that NF-κB activation can be involved in the induction of iNOS/NO. All changes were associated with a 2.9-fold decrease in the serum content of 25-hydroxyvitamin D3 and significant reduction of hepatic vitamin D3 receptor (VDR) expression that points reliably to vitamin D3 deficiency and failures in VDR signaling. Vitamin D3 co-administration (100 IU/rat, 30 days) prevented glucocorticoid-evoked abnormalities in hepatic tissue. In conclusion, prednisolone-induced liver disturbances were associated with the impairment of NF-κB/iNOS/NO responses that can be ameliorated by vitamin D3 treatment through VDR-mediated mechanisms.

The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.

PIO, a synthetic ligand for PPARγ, is used clinically to treat T2DM. However, little is known about its protective effects on endothelium and the underlying mechanisms. In this study, we sought to investigate the protective effects of PIO on endothelium and its probable mechanisms: 95% confluent wild type (WT) HUVECs and PPARγLow-HUVECs that we first injured with HG (33 mmol·L–1) were first pretreated with 10 μmol·L–1 of GW9662 for 30 min, and then treated the cells with different concentrations of PIO (5, 10, or 20 μmol·L–1) for 24 h. Finally, we measured the levels of NO, ET1, TNFα, and IL6 in the cell culture supernatant. These cells were then used to determine cell viability, caspase3 activity, the levels of IKKα/β mRNA, IKKα/β, and NFκB-p65. Severe dysfunction and activation of IKKα/β–NFκB signaling occurred after we exposed HUVECs to HG. Conversely, treatment with PIO significantly attenuated the dysfunction and the activation of IKKα/β–NFκB signaling induced by HG in a dose-dependent manner. Moreover, the protective effects of PIO were completely abrogated by GW9662 or down-regulation of PPARγ. Taken together, the results indicate that PIO protects HUVECs against the HG-induced dysfunction through the inhibition of IKKα/β–NFκB signaling mediated by PPARγ.

Background:Behçet’s Disease (BD) is a systemic vasculitis of unknown etiology[1]. Monocytes closely related to inflammation potentially contribute to BD’s pathogenesis. They are classified into three subsets: classical monocytes (CM), intermediate monocytes (IM) and non-classical monocytes (NCM). Abnormalities of monocyte subsets have been reported in many infectious, inflammatory and autoimmune diseases[2-6], but their implication in BD remains elusive.Objectives:To investigate the distribution, phenotypes and functions of monocyte subsets in BD and explore their roles in BD pathogenesis.Methods:The frequencies and phenotypes of monocyte subsets in BD and healthy controls (HC) were determined by flow cytometry, and their correlation with clinical parameters was analyzed. Intracellular cytokines and phosphorylated signal proteins [phosphorylated p65(p-p65) and phosphorylated p38(p-p38)] were determined in LPS-activated monocyte subsets by flow cytometry. Monocyte subsets of BD and HC were sorted and co-cultured with naïve CD4 + T cells, and Th1 cell frequencies were measured on day 5.Results:A higher IM (9.0±3.6 % vs. 4.5±2.0%, p<0.01) and lower NCM (2.6±1.2% vs. 4.2±2.0%, p<0.01) population in BD patients were noted. BD IM were positively correlated with CRP (r=0.5456, p<0.05), ESR (r=0.4683, p=0.05), and the serum level of TNF-a (r=0.7372, p<0.001) and IL-6(r=0.5013, p<0.05). BD NCM were negatively correlated with CRP (r=0.4822, p<0.05) and the serum level of IgM (r=-0.7830, p<0.001). Moreover, BD IM decreased (12.3±3.8% vs. 5.7±3.6%, p<0.05), while BD NCM increased (2.6±1.3% vs. 3.5±1.5%, p<0.01) after BD patients achieved remission. CD11b and CD64 expression on CM, IM and NCM in BD were enhanced. BD CM promoted TNF-a (61.0±11.4% vs 48.3±9.9%, p<0.05) and IL-6 (7.2±5.4% vs1.9±1.7%, p<0.05) production and facilitated Th1 differentiation. BD IM promoted IL-6 production (6.2±3.8% vs 2.6±1.6%, p<0.05). Furthermore, we demonstrated a higher level of p-p65 (12.8±2.9% vs 3.3±1.1%, p<0.01) in BD CM and increased p-p65 (3.2±0.6% vs 0.01±0.01%, p<0.01) and p-p38 (1.1±0.6% vs 0.03±0.01%, p<0.01) in BD IM.Conclusion:To our knowledge, our study is the first study on monocyte subsets in BD. Our data highlighted the aberrant populations of IM and CM in BD, potentially implicated in BD pathogenesis.References:[1]Ahmet, Gül, Pathogenesis of Behçet’s disease: autoinflammatory features and beyond, Semin. Immunopathol. 37 (2015) 413-418.[2]G.Fingerle, A.Pforte, B.Passlick, et al.The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients, Blood. 82 (1993) 3170-3176.[3]M.Moniuszko, A. Bodzenta-Lukaszyk, K. Kowal, et al. Enhanced frequencies of CD14++CD16+, but not CD14+CD16+, peripheral blood monocytes in severe asthmatic patients, Clin. Immunol. 130 (2009) 338-346.[4]M.D.Sanchez, Y.Garcia, C.Montes,et al.Functional and phenotypic changes in monocytes from patients with tuberculosis are reversed with treatment, Microbes. Infec. 8 (2006) 2492-2500.[5]S.Koch, T.Kucharzik, J.Heidemann,et al. Investigating the role of proinflammatory CD16+ monocytes in the pathogenesis of inflammatory bowel disease, Clin. Exp. Immunol. 161 (2010) 332-341.[6]H. Zhu, F. Hu, X. Sun,et al.CD16(+) Monocyte Subset Was Enriched and Functionally Exacerbated in Driving T-Cell Activation and B-Cell Response in Systemic Lupus Erythematosus, Front. immunol. 7 (2016) 512.Disclosure of Interests:None declared

Current treatments for Kaposi's Sarcoma (KS) and Primary Effusion Lymphoma (PEL) rely on systemic chemotherapeutics developed for non-virus-associated cancers that target DNA replication of all dividing cells. Other treatment methods aim at keeping immune system healthy and infection under control through surgery. All of the above approaches have low efficacy, high cost, and high risk of secondary malignancies especially in immuno-compromised patients. Hence, there is an emerging need to look for alternative treatment focused on KS or PEL host molecules, such as Lipoxins. Lipoxins are anti-inflammatory molecules that can target a variety of pro-inflammatory pathways of KS and PEL. Previous results from our lab have shown that level of ALX receptor (ALXR) does not change after Kaposi's Sarcoma Herpes Virus (KSHV) infection, leading to the potential use of Lipoxins to trigger anti-inflammatory and pro-apoptotic pathways as treatment of KS and PEL.In this study, we investigated downstream signaling in KSHV harboring body cavity B cell lymphoma (BCBL-1) cells induced by Lipoxin treatment to assess its pro-apoptotic effect. We treated 5–10×106 BCBL-1 cells with solvent control (EtOH), Lipoxin (100 mM), or Epilipoxin (100 mM) for 48 and 72 hrs. Downstream phosphorylation of Akt, NF-kB p65, and ERK were assessed using Western blotting and pro-apoptotic gene changes were detected using Real-Time PCR. Cell survival and cell cycle progression was assessed using BrdU FACS analysis. We found that Lipoxin and Epilipoxin treatment downregulated NF-kB and ERK activation via ALXR binding while Akt signaling was not affected. We also found that Lipoxin successfully upregulated pro-apoptotic genes such as BIM-1, BAX, BCL-10, and p53 compared to control. Lipoxin treatment also led to decreased S-phase progression and induction of apoptosis. In conclusion, our study suggests that Lipoxins have therapeutic potential for PEL and should be explored in KS and other PEL cell types.

Abstract Hematopoietic cell kinase (HCK) is a member of the SRC family of tyrosine kinases (SFKs). HCK transcription is aberrantly upregulated in Waldenström's Macroglobulinemia (WM) and Activated B-cell (ABC) subtype Diffuse Large B-cell Lymphoma (DLBCL) in response to activating mutations in MYD88 (Yang et al, Blood 2016). To clarify the mechanism responsible for the aberrant upregulation of HCK transcription inMYD88 mutated cells, we analyzed the promoter sequence of HCK using PROMO and identified consensus binding sites for transcription factors (AP1, NF-kB, STAT3, and IRF1) that are regulated by mutated MYD88 (Ngo et al, Nature 2011; Treon et al, NEJM 2012; Yang et al, Blood 2013; Juilland et al, Blood 2016; Yang et al, Blood 2016). We performed Chromatin Immuno-precipitation (ChIP) assays using ChIP grade antibodies to JunB, c-Jun, NF-kB-p65, STAT3 and IRF1 in MYD88 mutated WM (BCWM.1, MWCL-1) and ABC DLBCL (TMD-8, HBL-1, OCI-Ly3) cells that highly express HCK transcripts, as well as wild type MYD88 expressing GCB DLBCL (OCI-Ly7, OCI-Ly19) cells that show low HCK transcription. Following ChIP, a HCK promoter specific quantitative PCR assay was used to detect HCK promoter sequences. These studies showed that JunB, NF-kB-p65 and STAT3 bound more robustly to the HCK promoter in MYD88 mutated WM and ABC-DLBCL cells versus MYD88 wild type GCB DLBCL cell lines, while c-Jun bound more abundantly to the HCK promoter sequence in all DLBCL cell lines, regardless of MYD88 mutation status. In contrast c-Jun binding was low in MYD88 mutated WM cells. IRF1 binding to the HCK promoter was similar in all cell lines, regardless of the MYD88 mutation status. To further investigate HCK regulation, we developed an HCK promoter driven luciferase reporter vector (WT) with mutated AP-1 binding (AP1-mu-1~6), NF-kB binding (NF-kB-mu-1~5), and STAT3 binding (STAT3-mu) sites and investigated their impact on HCK promoter activity in MYD88 mutated BCWM.1 cells. We observed that mutation of AP1-mu-1,4,5,6; NF-kB-mu-1,4,5, as well as STAT3-mu binding sites greatly reduced HCK promoter activity, thereby supporting a role for AP-1, NF-kB and STAT3 transcription factors in HCK gene expression in MYD88 mutated cells. To further clarify the importance of these transcription factors in aberrant HCK gene expression in MYD88 mutated cells, we treated BCWM.1, MWCL-1, TMD-8 and HBL-1 cells with the AP-1 inhibitor SR 11302; NF-kB inhibitor QNZ; and the STAT3 inhibitor STA-21. Treatment of cells for 2 hours with SR 11302, QNZ, and STA-21 at sub-EC50 concentrations resulted in decreased HCK expression in MYD88 mutated all cell lines. Lastly, we investigated the contribution of BCR signaling to HCK transcription. BCWM.1, MWCL-1, TMD-8, and HBL-1 cells were treated with the Syk kinase inhibitor R406, and HCK transcription levels were then assessed. Differences in HCK expression were observed between MYD88 mutated WM and ABC DLBCL cells following R406, supporting a contributing role for BCR signaling in ABC DLBCL but not WM cells to HCK expression. Our data provide critical new insights into HCK regulation, and a framework for targeting pro-survival HCK signaling in WM and ABC DLBCL cells dependent on activating MYD88 mutations. Disclosures Castillo: Biogen: Consultancy; Otsuka: Consultancy; Millennium: Research Funding; Janssen: Honoraria; Abbvie: Research Funding; Pharmacyclics: Honoraria. Treon:Janssen: Consultancy; Pharmacyclics: Consultancy, Research Funding.

Tumbuhan jambu biji (Psidium guajava L var. pomifera) adalah salah satu tanaman obat-obatan yang sering dimanfaatkan oleh masyarakat khususnya di Indonesia. Tumbuhan yang termasuk ke dalam famili Myrtaceae tersebut memiliki khasiat sebagai antidiare, antioksidan, antiinflamasi, dan antimikroba. Penelitian ini bertujuan untuk mengetahui kandungan senyawa metabolit sekunder yang terdapat dalam daun jambu biji merah (Psidium guajava L. Var. Pomifera). Berdasarkan pengujian fitokimia yang telah dilakukan, menunjukkan bahwa daun kering positif mengandung senyawa steroid, saponin, fenol, dan tanin. Sedangkan pada daun segar positif mengandung senyawa alkaloid, steroid, saponin, fenol, dan tanin. Referensi : [1] S. S. H. Aponno V. J., Yamlean Y. V. P., “Uji Efektivitas Sediaan Gel Ekstrak Etanol Daun Jambu Biji (Psidium guajava Linn) terhadap Penyembuhan Luka yang Terinfeksi Bakteri Staphylococcus Aureus pada Kelinci (Orytolagus cuniculus),” PHARMACON, vol. 3, no. 3, pp. 279–286, 2014, doi: 10.35799/pha.3.2014.5400. [2] R. Rachmaniar, H. Kartamihardja, and Merry, “Pemanfaatan Buah Jambu Biji Merah (Psidium guajava Linn.) Sebagai Antioksidan Dalam Bentuk Granul Effervescent,” JSTFI Indones. J. Pharm. Sci. Technol., vol. 1, no. 5, pp. 1–20, 2016. [3] Z. S. Desiyana S. L., Husni A. M., “Uji Efektivitas Sedian Gel Fraksi Etil Asetat Daun Jambu Biji (Psidium Guajava Linn) terhadap Penyenmbuhan Luka Terbuka pada Mencit (Mus musculus).,” J. Nat., vol. 16, no. 2, pp. 23–32, 2016. [4] Rabbiyah F., “Pengaruh Pemberian Ekstrak Daun Jambu Biji (Psidium guajava Linn.) terhadap Pengikatan Trombosit pada Pasien Demam Berdarah Dengue,” J. Major., vol. 4, no. 7, pp. 91–96, 2015. [5] T. Handayani, Witjaksono, and K. U. Nugraheni, “Induksi Tetraploid Pada Tanaman Jambu Biji Merah (Psidium guajava L.) secara In Vitro,” J. Biol. Indones., vol. 13, no. 2, pp. 271–278, 2017, doi: 10.47349/jbi/13022017/271. [6] Y. Tampubolon R. T., “Pengaruh Formulasi Terhadap Sifat Fisik, Kimia, dan Organoleptik Effervescent Jambu Biji Merah (Psidium guajava var. Pomifera).,” J. Pangan dan Agroindustri, vol. 5, no. 3, pp. 27–37, 2017. [7] S. A. Ariyani A. M. D., Santoso I. S., “Analisa Profitalitas Usaha Tani Jambu Biji Getas Merah di Kabupaten Kendal,” Acromedia, vol. 35, no. 2, pp. 10–18, 2017. [8] I. S. W. Atmaja, Ismail Saleh, R. Eviyati, and D. Budirokhman, “Kajian Aplikasi Pupuk Kandang dan Pupuk Npk Terhadap Kualitas dan Mutu Jambu Biji Merah (Psidium guajava L.) Kultivar Getas pada Musim Kemarau,” J. Agrovigor, vol. 9, no. 2, pp. 111–117, 2016. [9] C. Dhyan, S. H. Sumarlan, and B. Susilo, “Pengaruh Pelapisan Lilin Lebah dan Suhu Penyimpanan Terhadap Kualitas Buah Jambu Biji (Psidium Guajava L.),” J. Bioproses Komod. Trop., vol. 2, no. 1, pp. 79–90, 2014. [10] W. N. Gunawan R., Susanto H. W., “Pengaruh Lama Pemanasan dan Konsentrasi Maizena terhadap Karakteristik Fisik, Kimia dan Organoleptik Lempok Jambu Biji Merah (Psidium Guajava L.),” J. Pangan dan Agroindustri, vol. 6, no. 1, pp. 1–11, 2018. [11] D. N. Maria and E. Zubaidah, “Pembuatan Velva Jambu Biji Merah Probiotik (Lactobacillus Acidophilus) Kajian Persentase Penambahan Sukrosa dan CMC,” J. Pangan dan Agroindustri, vol. 2, no. 4, pp. 18–28, 2014. [12] W. R. Andriani, “Efektivitas Mengkonsumsi Jus Apel Dibandingkan dengan Mengkonsumsi Jus Jambu Biji terhadap Penurunan Tingkat Halitosis,” AcTion Aceh Nutr. J., vol. 3, no. 2, pp. 164–171, 2018. [13] F. Nadifah, S. Fatimah, and L. Susanti, “Pengaruh Infusa Daun Jambu Biji (Psidium guajava Linn.) Terhadap Pertumbuhan Bakteri Escherichia coli Secara In Vitro,” J. Heal., vol. 2, no. 2, pp. 65–68, 2015, doi: 10.30590/vol2-no2-p65-68. [14] I. B. Wicaksono and M. Ulfah, “Uji Aktivitas Antioksidan Kombinasi Ekstrak Etanol Daun Sirsak (Annona muricata L.) dan Daun Jambu Biji (Psidium guajava L.) dengan Metode DPPH (2,2-difenil-1-pikrihidrazil),” Inov. Tek. Kim., vol. 2, no. 1, pp. 44–48, 2017. [15] I. Hartati, S. Nurfaizin, Suwardiyono, and L. Kurniasari, “Ekstraksi Gelombang Mikro Terpenoid Daun Surian (Toona sureni Merr),” Inov. Tek. Kim., vol. 1, no. 2, pp. 98–103, 2016. [16] A. U. Mulyanto S., Sumardianto, “Pengaruh Penambahan Ekstrak Daun Jambu Biji Merah (Psidium guajava) terhadap Daya Simpan Ikan Nila Merah (Oreochromis niloticus) pada Suhu Dingin,” J. Pengolah. dan Bioteknol. Has. Perikan., vol. 6, no. 4, pp. 1–7, 2018. [17] H. Setiawan, L. B. Utami, and M. Zulfikar, “Serbuk Daun Jambu Biji Memperbaiki Performans Pertumbuhan dan Morfologi Duodenum Ayam Jawa Super,” J. Vet., vol. 19, no. 4, pp. 554–562, 2018. [18] H. Halimatussakdiah, U. Amna, and P. Wahyuningsih, “Preliminary Phytochemical Analysis and Larvicidal Activity of Edible Fern (Diplazium esculentum (Retz.) Sw.) Extract against Culex,” J. Nat., vol. 18, no. 3, pp. 141–146, 2018, doi: 10.24815/jn.v0i0.11335. [19] R. Ningrum, E. Purwanti, and Sukarsono, “Identifikasi Senyawa Alkaloid dari Batang Karamunting (Rhodomyrtus tomentosa) Sebagai Bahan Ajar Biologi Untuk SMA Kelas X,” J. Pendidik. Biol. Indinesia, vol. 2, no. 3, pp. 231–236, 2016. [20] A. R. Nasrudin., Wahyono., Mustofa., Saridarti, “Isolasi Senyawa dari Kulit Akar Sengugun (Elerdenrum serratum L. Moon),” J. Ilm. Farm., vol. 6, no. 3, pp. 332–337, 2017. [21] N. Hidayah, “Pemanfaatan Senyawa Metabolit Sekunder Tanaman (Tanin dan Saponin) dalam Mengurangi Emisi Metan Ternak Ruminansia,” J. Sain Peternak. Indones., vol. 1, no. 2, pp. 89–98, 2016, doi: 10.31186/jspi.id.11.2.89-98. [22] Z. D. Novitasari, E. 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Background:Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by bone destruction[1]. Chemokine signaling by skeletal cells or by other cells of the bone marrow niche regulates bone formation and resorption[2]. Recent studies have found that CXCL7 enhanced the osteoclast formation in mouse bone marrow cells[3, 4]. Whether CXCL7 plays a role in human osteoclastogenesis especially in RA patients remains unclear.Objectives:To examine the functional role of CXCL7 in the induction of osteoclastogenesis in RA.Methods:The level of CXCL7 in CD14+monocyte supernatant was assessed via enzyme-linked immunosorbent assay. Osteoclastogenesis of CD14+monocyte from RA patients and healthy donors were evaluated by TRAP staining and F-actin ring immunofluorescence. Bone resorption pit was observed by scanning electron microscopy. We performed quantitative reverse transcription polymerase chain reaction (RT-PCR) to detect changes in osteoclast markers. RAW264.7 macrophages were also used to investigate specific signaling pathway by which CXCL7 stimulated during osteoclast formation.Results:CXCL7 level in CD14+monocyte supernatant from RA patients (5690 ±627.05 pg/ml) was significantly higher than that in healthy controls (2301 ±535.52 pg/ml) (n=5, P<0.001). In the presence of M-CSF and RANKL, CXCL7 promoted osteoclast formation(Figure 1A and B) and increased bone resorption area(Figure 1C) of CD14+monocyte from healthy donors in the low concentration (10ng/ml) group (n=3, p < 0.05). While in high concentration of CXCL7 (50ng/ml) group, there were no significant changes in the number of osteoclasts. Transcription level of the osteoclast markers RANK, cathepsin K, and MMP-9 was significantly increased in the CXCL7 (10 ng/mL) group after 3 days in the presence of M-CSF and sRANKL (n=3, p < 0.05). When using CD14+ monocyte from RA patients, the optimal concentration of CXCL7 was 50ng/ml, which significantly increased the number of osteoclasts (Figure 2A and B)and bone resorption area (Figure 2C) (n=3, p < 0.01). Flow cytometry analysis revealed that a higher proportion of CD14+monocytes expressed CXCR2 from healthy donors than those from RA patients (n=6, p < 0.01). Consistent with the results obtained in CD14+monocytes, the effects of exogenous CXCL7 on osteoclast formation were also observed in RAW264.7 cells (p < 0.01). The addition of CXCL7 dramatically promoted phosphorylation ERK1/2 in RAW264.7 cells, but it did not affect the phosphorylation of P65.Conclusion:CXCL7 level in CD14+monocyte supernatant was higher in RA patients than that of healthy donors. CXCL7 promoted osteoclastogenesis in CD14+monocyte both from RA patients and healthy donors. CXCL7 could be a potential therapeutic target for bone destruction in RA.References:[1] McInnes, I.B. and G. Schett, The pathogenesis of rheumatoid arthritis. N Engl J Med, 2011. 365(23): p. 2205-19.[2] Brylka, L.J. and T. Schinke, Chemokines in Physiological and Pathological Bone Remodeling. Front Immunol, 2019. 10: p. 2182.[3] Nakao, K., et al., IGF2 modulates the microenvironment for osteoclastogenesis. Biochem Biophys Res Commun, 2009. 378(3): p. 462-6.[4] Goto, Y., et al., CXCR4(+) CD45(-) Cells are Niche Forming for Osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 Signaling Pathways in Bone Marrow. Stem Cells, 2016. 34(11): p. 2733-2743.Acknowledgments :We gratefully thank the Medical Research Center of Peking University Third Hospital for providing experimental equipment and technical support.Disclosure of Interests:None declared