Journal articles on the topic 'Peripheral challenges and inflammation'
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1
Ferrari, Carina C., and Rodolfo Tarelli. "Parkinson's Disease and Systemic Inflammation." Parkinson's Disease 2011 (2011): 1–9. http://dx.doi.org/10.4061/2011/436813.
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Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in thesubstantia nigra(SN). Peripheral inflammation can transform the “primed” microglia into an “active” state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease.
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Blomqvist, Anders, and David Engblom. "Neural Mechanisms of Inflammation-Induced Fever." Neuroscientist 24, no. 4 (March 20, 2018): 381–99. http://dx.doi.org/10.1177/1073858418760481.
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Fever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis. Here, we review the different hypotheses on how the presence of peripherally released pyrogenic substances can be signaled to the brain to elicit fever. We conclude that there is unequivocal evidence for a humoral signaling pathway by which proinflammatory cytokines, through their binding to receptors on brain endothelial cells, evoke fever by eliciting prostaglandin E2 synthesis in these cells. The evidence for a role for other signaling routes for fever, such as signaling via circumventricular organs and peripheral nerves, as well as transfer into the brain of peripherally synthesized prostaglandin E2 are yet far from conclusive. We also review the efferent limb of the pyrogenic pathways. We conclude that it is well established that prostaglandin E2 binding in the preoptic hypothalamus produces fever by disinhibition of presympathetic neurons in the brain stem, but there is yet little understanding of the mechanisms by which factors such as nutritional status and ambient temperature shape the response to the peripheral immune challenge.
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López-Ornelas, Adolfo, Adriana Jiménez, Gilberto Pérez-Sánchez, Citlali Ekaterina Rodríguez-Pérez, Alejandro Corzo-Cruz, Iván Velasco, and Enrique Estudillo. "The Impairment of Blood-Brain Barrier in Alzheimer’s Disease: Challenges and Opportunities with Stem Cells." International Journal of Molecular Sciences 23, no. 17 (September 4, 2022): 10136. http://dx.doi.org/10.3390/ijms231710136.
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Alzheimer’s disease (AD) is the most common neurodegenerative disorder and its prevalence is increasing. Nowadays, very few drugs effectively reduce AD symptoms and thus, a better understanding of its pathophysiology is vital to design new effective schemes. Presymptomatic neuronal damage caused by the accumulation of Amyloid β peptide and Tau protein abnormalities remains a challenge, despite recent efforts in drug development. Importantly, therapeutic targets, biomarkers, and diagnostic techniques have emerged to detect and treat AD. Of note, the compromised blood-brain barrier (BBB) and peripheral inflammation in AD are becoming more evident, being harmful factors that contribute to the development of the disease. Perspectives from different pre-clinical and clinical studies link peripheral inflammation with the onset and progression of AD. This review aims to analyze the main factors and the contribution of impaired BBB in AD development. Additionally, we describe the potential therapeutic strategies using stem cells for AD treatment.
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Vara, Sarina, Ioannis Kypraios, Ankur Thapar, Constantinos Kyriakides, and Shiva Dindyal. "Challenges in investigating Peripheral Vascular Disease in patients with Diabetes and Cardiovascular Diseases." International Journal of cardiodiabetes 1, no. 2 (October 1, 2022): 98–99. http://dx.doi.org/10.52964/ijcd.0015.
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Given the increasing prevalence of diabetes, with cardiovascular disease representing the principle cause of death and morbidity amongst diabetics, it is imperative that early investigation and then intervention is achieved. Diabetic patients are at increased risk of peripheral arterial disease (PAD), with an earlier onset and a more severe and diffuse manifestation often being seen. The key factors in diabetic arteriopathy include vascular smooth vessel dysfunction, inflammation, hypercoagulability and endothelial dysfunction. Moreover, the presence of PAD is a marker of generalised atherosclerosis and is a strong indicator of increased morbidity and mortality due to cardiovascular ischaemic events, with the risk of atherothrombotic events increasing in the presence of concomitant diabetes.
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Davis, Michael S., Chris M. Royer, Mark Payton, and Brian Buttress. "Modeling the acute- and late-phase responses to peripheral airway cooling and desiccation." Journal of Applied Physiology 93, no. 1 (July 1, 2002): 195–200. http://dx.doi.org/10.1152/japplphysiol.00074.2002.
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Acute bronchoconstriction after isocapnic hyperpnea can be produced in most asthmatic individuals. However, the existence of a late-phase response is less certain. We used a canine model of isocapnic hyperpnea to test the hypothesis that this discrepancy is due to differences in the challenge threshold for the responses. Acute-phase and late-phase bronchoconstriction was measured in nine dogs after peripheral airway exposure to unconditioned air. Additionally, bronchoalveolar lavage fluid (BALF) was obtained during the late-phase response. The acute-phase response was a polynomial function with a decreasing slope at higher challenges, whereas the late-phase response suggested that a minimum threshold of challenge severity was needed to produce late-phase bronchoconstriction. BALF leukocyte and eicosanoid concentrations had linear relationships with challenge severity. Our data support the hypothesis that acute- and late-phase posthyperpnea responses have different dose-response relationships, a fact that may explain the frequent lack of a late-phase response. However, our data suggest that mild inflammation can be induced with relatively lower challenge severity.
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Marottoli, Felecia M., Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, and Leon M. Tai. "Peripheral Inflammation, Apolipoprotein E4, and Amyloid-β Interact to Induce Cognitive and Cerebrovascular Dysfunction." ASN Neuro 9, no. 4 (July 14, 2017): 175909141771920. http://dx.doi.org/10.1177/1759091417719201.
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Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 ( APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of 5 Familial Alzheimer’s disease (5xFAD) mutations. Here, we utilized EFAD carriers [5xFAD+/−/ APOE+/+ (EFAD+)] and noncarriers [5xFAD−/−/ APOE+/+ (EFAD−)] to compare the effects of peripheral inflammation in the presence or absence of human Aβ overproduction. Low-level, chronic repeated peripheral inflammation was induced in EFAD mice via systemic administration of lipopolysaccharide (LPS; 0.5 mg/kg/wk i.p.) from 4 to 6 months of age. In E4FAD+ mice, peripheral inflammation caused cognitive deficits and lowered post-synaptic protein levels. Importantly, cerebrovascular deficits were observed in LPS-challenged E4FAD+ mice, including cerebrovascular leakiness, lower vessel coverage, and cerebral amyloid angiopathy-like Aβ deposition. Thus, APOE4, Aβ, and peripheral inflammation interact to induce cerebrovascular damage and cognitive deficits.
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Cloots, Roy H. E., Selvakumari Sankaranarayanan, Chiel C. de Theije, Matthew E. Poynter, Els Terwindt, Paul van Dijk, Theodorus B. M. Hakvoort, Wouter H. Lamers, and S. Eleonore Köhler. "Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice." American Journal of Physiology-Lung Cellular and Molecular Physiology 305, no. 5 (September 1, 2013): L364—L376. http://dx.doi.org/10.1152/ajplung.00341.2012.
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Asthma is a chronic inflammatory disease of the small airways, with airway hyperresponsiveness (AHR) and inflammation as hallmarks. Recent studies suggest a role for arginase in asthma pathogenesis, possibly because arginine is the substrate for both arginase and NO synthase and because NO modulates bronchial tone and inflammation. Our objective was to investigate the importance of increased pulmonary arginase 1 expression on methacholine-induced AHR and lung inflammation in a mouse model of allergic asthma. Arginase 1 expression in the lung was ablated by crossing Arg1 fl/fl with Tie2Cre tg/− mice. Mice were sensitized and then challenged with ovalbumin. Lung function was measured with the Flexivent. Adaptive changes in gene expression, chemokine and cytokine secretion, and lung histology were quantified with quantitative PCR, ELISA, and immunohistochemistry. Arg1 deficiency did not affect the allergic response in lungs and large-airway resistance, but it improved peripheral lung function (tissue elastance and resistance) and attenuated adaptive increases in mRNA expression of arginine-catabolizing enzymes Arg2 and Nos2, arginine transporters Slc7a1 and Slc7a7, chemokines Ccl2 and Ccl11, cytokines Tnfa and Ifng, mucus-associated epithelial markers Clca3 and Muc5ac, and lung content of IL-13 and CCL11. However, expression of Il4, Il5, Il10, and Il13 mRNA; lung content of IL-4, IL-5, IL-10, TNF-α, and IFN-γ protein; and lung pathology were not affected. Correlation analysis showed that Arg1 ablation disturbed the coordinated pulmonary response to ovalbumin challenges, suggesting arginine (metabolite) dependence of this response. Arg1 ablation in the lung improved peripheral lung function and affected arginine metabolism but had little effect on airway inflammation.
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d’Alessandro, Elisa, Christian Becker, Wolfgang Bergmeier, Christoph Bode, Joshua H. Bourne, Helena Brown, Harry R. Buller, et al. "Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis." Thrombosis and Haemostasis 120, no. 04 (April 2020): 538–64. http://dx.doi.org/10.1055/s-0040-1708035.
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AbstractThrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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Tebbutt, Scott J., Jian-Qing He, Amrit Singh, Casey P. Shannon, Jian Ruan, and Chris Carlsten. "Transcriptional Changes of Blood Eosinophils after Methacholine Inhalation Challenge in Asthmatics." Genomics Insights 5 (January 2012): GEI.S9125. http://dx.doi.org/10.4137/gei.s9125.
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Background Methacholine challenge is commonly used within the asthma diagnostic algorithm. Methacholine challenge has recently been shown to induce airway remodelling in asthma via bronchoconstriction, without additional airway inflammation. We evaluated the effect of methacholine-induced bronchoconstriction on the peripheral whole-blood transcriptome. Methods Fourteen males with adult-onset, occupational asthma, 26–77 years of age, underwent methacholine inhalation challenges. The concentration of methacholine eliciting a ≥20% fall in FEV1 (PC20) was determined. Blood was collected immediately prior to and two hours after challenge. Complete blood counts and leukocyte differentials were obtained. Transcriptome analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST arrays. Data were analyzed using robust LEMMA and SAM. The cell-specific Significance Analysis of Microarrays (csSAM) algorithm was used to deconvolute the gene expression data according to cell type. Results Microarray pathway analysis indicated that inflammatory processes were differentially affected. CsSAM identified 1,559 transcripts differentially expressed (all down-regulated) between pre- and post-methacholine in eosinophils at a false discovery cutoff of 10%. Notable changes included the GOLGA5 and METTL2B genes and the protein ubiquitination and CCR3 pathways. Conclusions We demonstrated significant changes in the peripheral blood eosinophil-specific transcriptome of asthmatics two hours after methacholine challenge. CCR3 and protein ubiquitination pathways are both significantly down-regulated.
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Levy, Ryan M., Jose M. Prince, Runkuan Yang, Kevin P. Mollen, Hong Liao, Gregory A. Watson, Mitchell P. Fink, Yoram Vodovotz, and Timothy R. Billiar. "Systemic inflammation and remote organ damage following bilateral femur fracture requires Toll-like receptor 4." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291, no. 4 (October 2006): R970—R976. http://dx.doi.org/10.1152/ajpregu.00793.2005.
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Extensive soft tissue injury and bone fracture are significant contributors to the initial systemic inflammatory response in multiply injured patients. Systemic inflammation can lead to organ dysfunction remote from the site of traumatic injury. The mechanisms underlying the recognition of peripheral injury and the subsequent activation of the immune response are unknown. Toll-like receptors (TLRs) recognize microbial products but also may recognize danger signals released from damaged tissues. Here we report that peripheral tissue trauma initiates systemic inflammation and remote organ dysfunction. Moreover, this systemic response to a sterile local injury requires toll-like receptor 4 (TLR4). Compared with wild-type (C3H/HeOuJ) mice, TLR4 mutant (C3H/HeJ) mice demonstrated reduced systemic and hepatic inflammatory responses to bilateral femur fracture. Trauma-induced nuclear factor (NF)-κB activation in the liver required functional TLR4 signaling. CD14−/− mice failed to demonstrate protection from fracture-induced systemic inflammation and hepatocellular injury. Therefore, our results also argue against a contribution of intestine-derived LPS to this process. These findings identify a critical role for TLR4 in the rapid recognition and response pathway to severe traumatic injury. Application of these findings in an evolutionary context suggests that multicellular organisms have evolved to use the same pattern recognition receptor for surviving traumatic and infectious challenges.
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Bista and Imlach. "Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain." Medicines 6, no. 3 (August 22, 2019): 91. http://dx.doi.org/10.3390/medicines6030091.
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Trigeminal neuropathic pain is a chronic pain condition caused by damage or inflammation of the trigeminal nerve or its branches, with both peripheral and central nervous system dysfunction contributing to the disorder. Trigeminal pain conditions present with diagnostic and therapeutic challenges to healthcare providers and often require multiple therapeutic approaches for pain reduction. This review will provide the overview of pathophysiology in peripheral and central nociceptive circuits that are involved in neuropathic pain conditions involving the trigeminal nerve and the current therapeutics that are used to treat these disorders. Recent advances in treatment of trigeminal pain, including novel therapeutics that target ion channels and receptors, gene therapy and monoclonal antibodies that have shown great promise in preclinical studies and clinical trials will also be described.
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Wang, Guoshun, and Hang Pong Ng. "Myeloid CFTR Loss-of-function Causes Persistent Neutrophilic Inflammation in Cystic Fibrosis." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 187.33. http://dx.doi.org/10.4049/jimmunol.202.supp.187.33.
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Abstract Persistent neutrophilic inflammation is a hallmark manifestation of cystic fibrosis (CF). However, the mechanism underlying this phenomenal clinical symptom remains incompletely understood. Here we report a pivotal role of CFTR in myeloid immune cells in control of neutrophilic inflammation. Myeloid CFTR-Knockout (Mye-Cftr−/−) mice and Wild-type (WT) mice were challenged peritoneally with zymosan at different doses. The lethal-dose challenge resulted in significantly higher mortality in Mye-Cftr−/− mice, indicating an intrinsic defect in host protection against inflammation in CF. The sub-lethal-dose challenge demonstrated an impaired resolution of inflammation in Mye-Cftr−/− mice, reflected by persistent neutrophilic inflammation, and hyper-inflammation with significantly higher levels of pro-inflammatory cytokines, including the neutrophil-recruiting chemokines MIP-2 and KC, which led to excessive neutrophil recruitment in vivo. Pulmonary challenge with zymosan confirmed the peritoneal finding. To determine the major types of cells responsible for the over-recruitment of neutrophils, zymosan-elicited peritoneal neutrophils and macrophages from Mye-Cftr−/− and WT mice were FACS-sorted and cultured ex vivo. The CF neutrophils produced significantly more neutrophil chemokine MIP-2. Moreover, peripheral blood neutrophils and monocytes from Mye-Cftr−/− and WT mice were cultured and stimulated with zymosan in vitro. Similarly, the CF neutrophils produced significantly more MIP-2. These data altogether suggest that CFTR dysfunction in myeloid immune cells leads to excessive neutrophil recruitment, thus serving as a mechanism for the long-observed neutrophilic inflammation in CF.
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Vlassara, Helen, and Gary E. Striker. "The Role of Advanced Glycation End-products in the Etiology of Insulin Resistance and Diabetes." US Endocrinology 06, no. 01 (2010): 14. http://dx.doi.org/10.17925/use.2010.06.1.14.
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Despite new and effective drug therapies, insulin resistance (IR) and type 2 diabetes and its complications remain major medical challenges. It is known that IR, often associated with overnutrition and obesity, results from elevated oxidant stress (OS) and chronic inflammation. Less widely known is that a major cause for this inflammation is excessive consumption of advanced glycation end-products (AGEs) by the citizens of developed countries. AGEs, which were largely thought as oxidative derivatives resulting from diabetic hyperglycemia, are increasingly seen as a potential risk factor for islet β-cell injury, peripheral IR, and diabetes. This article will discuss the relationships between exogenous AGEs, chronic inflammation, IR, and type 2 diabetes. We present new insights on the failure of innate immune defense mechanisms under chronic oxidant overload, which increase susceptibility to IR and type 2 diabetes and its complications. Finally, we describe evidence on AGE restriction, a new non-pharmacologic intervention, which effectively reduces persistent IR, restores innate immune functions, and, thus, optimizes current antidiabetic drug therapies.
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Kerasnoudis, Antonios. "The Role of Neuromuscular Ultrasound when Diagnosing Chronic Inflammatory Demyelinating Polyneuropathy." US Neurology 09, no. 01 (2013): 52. http://dx.doi.org/10.17925/usn.2013.09.01.52.
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Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired immune-mediated inflammatory disorder of the peripheral nervous system. The diagnosis is based in classic cases, on the distribution pattern of the neurologic semiology, and pathologic changes of nerve conduction studies (NCS). However, in cases with subtle clinical presentation, an extended diagnostic workup may be needed (cerebrospinal fluid examination, laboratory tests, nerve biopsy). NCS remain fundamental for the diagnosis, follow up, and measurement of response to immune-treatment in CIDP. However, new challenges arose on how best to acquire a static and dynamic imaging of the peripheral nerves, with the aim of providing a holistic approach to the nerve impairment. According to the literature, neuromuscular ultrasound is able to detect in cases of CIDP thickened or swollen roots, peripheral nerves, or brachial plexus, findings that are consistent with ongoing inflammation. This review provides a timely update on the nerve ultrasound findings of CIDP and future possibilities of neuromuscular ultrasound are also discussed.
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Kerasnoudis, Antonios. "The Role of Neuromuscular Ultrasound in the Diagnostic of the Chronic Inflammatory Demyelinating Polyneuropathy." European Neurological Review 8, no. 1 (2012): 62. http://dx.doi.org/10.17925/enr.2013.08.01.62.
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Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired immune-mediated inflammatory disorder of the peripheral nervous system. The diagnosis is based in classic cases, on the distribution pattern of the neurological semiology and pathological changes of nerve conduction studies (NCS). However, in cases with subtle clinical presentation, an extended diagnostic workup may be needed (cerebrospinal fluid examination, laboratory tests, nerve biopsy). NCS remain fundamental for the diagnosis, follow-up and measurement of response to immunetreatment in CIDP. However, new challenges arose on how best to acquire a static and dynamic imaging of the peripheral nerves, with the aim of providing a holistic approach to the nerve impairment. According to the literature, neuromuscular ultrasound is able to detect in cases of CIDP thickened or swollen roots, peripheral nerves or brachial plexus, findings that are consistent with ongoing inflammation. This review provides a timely update on the nerve ultrasound findings of CIDP and future possibilities of neuromuscular ultrasound are also discussed.
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Moiseev, S., P. Novikov, S. Gulyaev, E. Kuznetsova, T. Shevtsova, I. Shafieva, and O. Bugrova. "Ankylosing spondylitis: diagnostic challenges and efficacy of upadacitinib." Clinical pharmacology and therapy 31, no. 4 (November 13, 2021): 62–70. http://dx.doi.org/10.32756/0869-5490-2021-4-62-70.
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Ankylosing spondilitis (AS) is a relatively common disease mainly affecting young males and presenting with chronic inflammation of the spine and the sacroiliac joints. AS is one of the forms of axial spondyloarthritis (SpA). Diagnosis of AS is usually delayed on average by 8-10 years from the first symptoms. SpA should be considered both in males and females who present with chronic low back pain starting before the age of 45 years and at least one additional factor (inflammatory back pain, HLA-B27, sacroileitis, peripheral arthritis, enthesitis, dactylitis, psoriasis, uveitis, inflammatory bowel disease, family history for SpA, elevated ESR and/or C-reactive protein, and good response to NSAIDs). Such patients should be referred to rheumatologist. MRI improves early diagnosis of AS since it detects inflammatory changes, which precede structural damage of the sacroiliac joints (nonradiographic SpA). Physical exercises and NSAIDs are the first-line treatment for AS, whereas TNF and interleukin-17 inhibitors are widely used as a second-line therapy. Upadacitinib is the first JAK-inhibitor that was approved for the treatment of active AS in adult patients who have responded inadequately to conventional therapy. The authors discuss clinical cases demonstrating efficacy of upadacinitib in patients with AS.
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Visentin, Ana Paula Vargas, Rafael Colombo, Ellen Scotton, Débora Soligo Fracasso, Adriane Ribeiro da Rosa, Catia Santos Branco, and Mirian Salvador. "Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges." Oxidative Medicine and Cellular Longevity 2020 (April 14, 2020): 1–20. http://dx.doi.org/10.1155/2020/2972968.
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The prevalence of psychiatric disorders has increased in recent years. Among existing mental disorders, major depressive disorder (MDD) has emerged as one of the leading causes of disability worldwide, affecting individuals throughout their lives. Currently, MDD affects 15% of adults in the Americas. Over the past 50 years, pharmacotherapy, psychotherapy, and brain stimulation have been used to treat MDD. The most common approach is still pharmacotherapy; however, studies show that about 40% of patients are refractory to existing treatments. Although the monoamine hypothesis has been widely accepted as a molecular mechanism to explain the etiology of depression, its relationship with other biochemical phenomena remains only partially understood. This is the case of the link between MDD and inflammation, mitochondrial dysfunction, and oxidative stress. Studies have found that depressive patients usually exhibit altered inflammatory markers, mitochondrial membrane depolarization, oxidized mitochondrial DNA, and thus high levels of both central and peripheral reactive oxygen species (ROS). The effect of antidepressants on these events remains unclear. Nevertheless, the effects of ROS on the brain are well known, including lipid peroxidation of neuronal membranes, accumulation of peroxidation products in neurons, protein and DNA damage, reduced antioxidant defenses, apoptosis induction, and neuroinflammation. Antioxidants such as ascorbic acid, tocopherols, and coenzyme Q have shown promise in some depressive patients, but without consensus on their efficacy. Hence, this paper provides a review of MDD and its association with inflammation, mitochondrial dysfunction, and oxidative stress and is aimed at thoroughly discussing the putative links between these events, which may contribute to the design and development of new therapeutic approaches for patients.
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Jans, Lennart, Anne Jurik, Iwona Sudoł-Szopińska, Claudia Schueller-Weidekamm, Iris Eshed, and Winston Rennie. "Anterior Chest Wall in Axial Spondyloarthritis: Imaging, Interpretation, and Differential Diagnosis." Seminars in Musculoskeletal Radiology 22, no. 02 (April 2018): 197–206. http://dx.doi.org/10.1055/s-0038-1639472.
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AbstractAnterior chest wall (ACW) inflammation is not an uncommon finding in patients with axial spondyloarthritis (ax-SpA) and reportedly occurs in 26% of these patients. Radiologists may only be familiar with spinal and peripheral joint imaging, possibly due to the inherent challenges of ACW imaging on some cross-sectional imaging modalities. Knowledge of relevant joint anatomy and the location of sites of inflammation allows the interpreting radiologist to better plan appropriate imaging tests and imaging planes. Accurate assessment of disease burden, sometimes in the absence of clinical findings, may alert the treating rheumatologist, allowing a better estimation of disease burden, increased accuracy of potential imaging scoring systems, and optimize assessment and response to treatment. This article reviews salient anatomy and various imaging modalities to optimize diagnosis, important differential diagnoses, and the interpretation of ACW imaging findings in ax-SpA.
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Von Essen, Susanna G., Dennis P. O'Neill, Sandra McGranaghan, Stephen A. Olenchock, and Stephen I. Rennard. "Neutrophilic Respiratory Tract Inflammation and Peripheral Blood Neutrophilia After Grain Sorghum Dust Extract Challenge." Chest 108, no. 5 (November 1995): 1425–33. http://dx.doi.org/10.1378/chest.108.5.1425.
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Méndez-Barbero, Nerea, Carmen Gutiérrez-Muñoz, Rafael Blázquez-Serra, Jose Martín-Ventura, and Luis Blanco-Colio. "Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK)/Fibroblast Growth Factor-Inducible 14 (Fn14) Axis in Cardiovascular Diseases: Progress and Challenges." Cells 9, no. 2 (February 11, 2020): 405. http://dx.doi.org/10.3390/cells9020405.
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Cardiovascular diseases (CVD) are the leading cause of mortality in Western countries. CVD include several pathologies, such as coronary artery disease, stroke, peripheral artery disease, and aortic aneurysm, among others. All of them are characterized by a pathological vascular remodeling in which inflammation plays a key role. Interaction between different members of the tumor necrosis factor superfamily and their cognate receptors induce several biological actions that may participate in CVD. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), are abundantly expressed during pathological cardiovascular remodeling. The TWEAK/Fn14 axis controls a variety of cellular functions, such as proliferation, differentiation, and apoptosis, and has several biological functions, such as inflammation and fibrosis that are linked to CVD. It has been demonstrated that persistent TWEAK/Fn14 activation is involved in both vessel and heart remodeling associated with acute and chronic CVD. In this review, we summarized the role of the TWEAK/Fn14 axis during pathological cardiovascular remodeling, highlighting the cellular components and the signaling pathways that are involved in these processes.
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Biesmans, Steven, Liam J. R. Matthews, Jan A. Bouwknecht, Patrick De Haes, Niels Hellings, Theo F. Meert, Rony Nuydens, and Luc Ver Donck. "Systematic Analysis of the Cytokine and Anhedonia Response to Peripheral Lipopolysaccharide Administration in Rats." BioMed Research International 2016 (2016): 1–14. http://dx.doi.org/10.1155/2016/9085273.
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Inflammatory processes may cause depression in subsets of vulnerable individuals. Inflammation-associated behavioral changes are commonly modelled in rodents by administration of bacterial lipopolysaccharide (LPS). However, the time frame in which immune activation and depressive-like behavior occur is not very clear. In this study, we showed that systemic administration of LPS robustly increased circulating levels of corticosterone, leptin, pro- and anti-inflammatory cytokines, and chemokines. Serum concentrations of most analytes peaked within the first 6 h after LPS injection and returned to baseline values by 24 h. Chemokine levels, however, remained elevated for up to 96 h. Using an optimized sucrose preference test (SPT) we showed that sickness behavior was present from 2 to 24 h. LPS-induced anhedonia, as measured by decreased sucrose preference, lasted up to 96 h. To mimic the human situation, where depression develops after chronic inflammation, rats were preexposed to repeated LPS administration or subchronic restraint stress and subsequently challenged with LPS. While these procedures did not increase the duration of anhedonia, our results do indicate that inflammation may cause depressive symptoms such as anhedonia. Using our SPT protocol, more elaborate rodent models can be developed to study the mechanisms underlying inflammation-associated depression in humans.
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Faustino, Lucas, Daniel Mucida, Alexandre Castro Keller, Jocelyne Demengeot, Karina Bortoluci, Luiz Roberto Sardinha, Maisa Carla Takenaka, Alexandre Salgado Basso, Ana Maria Caetano Faria, and Momtchilo Russo. "Regulatory T Cells Accumulate in the Lung Allergic Inflammation and Efficiently Suppress T-Cell Proliferation but Not Th2 Cytokine Production." Clinical and Developmental Immunology 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/721817.
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Foxp3+CD25+CD4+regulatory T cells are vital for peripheral tolerance and control of tissue inflammation. In this study, we characterized the phenotype and monitored the migration and activity of regulatory T cells present in the airways of allergic or tolerant mice after allergen challenge. To induce lung allergic inflammation, mice were sensitized twice with ovalbumin/aluminum hydroxide gel and challenged twice with intranasal ovalbumin. Tolerance was induced by oral administration of ovalbumin for 5 consecutive days prior to OVA sensitization and challenge. We detected regulatory T cells (Foxp3+CD25+CD4+T cells) in the airways of allergic and tolerant mice; however, the number of regulatory T cells was more than 40-fold higher in allergic mice than in tolerant mice. Lung regulatory T cells expressed an effector/memory phenotype (CCR4highCD62LlowCD44highCD54highCD69+) that distinguished them from naive regulatory T cells (CCR4intCD62LhighCD44intCD54intCD69−). These regulatory T cells efficiently suppressed pulmonary T-cell proliferation but not Th2 cytokine production.
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Nürnberger, Franz, Daniela Ott, Rebecca Claßen, Christoph Rummel, Joachim Roth, and Stephan Leisengang. "Systemic Lipopolysaccharide Challenge Induces Inflammatory Changes in Rat Dorsal Root Ganglia: An Ex Vivo Study." International Journal of Molecular Sciences 23, no. 21 (October 28, 2022): 13124. http://dx.doi.org/10.3390/ijms232113124.
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Inflammatory processes within the peripheral nervous system (PNS) are associated with symptoms of hyperalgesia and allodynia. Pro-inflammatory mediators, such as cytokines or prostaglandins, modulate the excitability of nociceptive neurons, called peripheral sensitization. Here, we aimed to examine if previously reported effects of in vitro stimulation with lipopolysaccharide (LPS) on primary cell cultures of dorsal root ganglia (DRG) reflect changes in a model of LPS-induced systemic inflammation in vivo. Male rats were intraperitoneally injected with LPS (100 µg/kg) or saline. Effects of systemic inflammation on expression of inflammatory mediators, neuronal Ca2+ responses, and activation of inflammatory transcription factors in DRG were assessed. Systemic inflammation was accompanied by an enhanced expression of pro-inflammatory cytokines and cyclooxygenase-2 in lumbar DRG. In DRG primary cultures obtained from LPS-treated rats enhanced neuronal capsaicin-responses were detectable. Moreover, we found an increased activation of inflammatory transcription factors in cultured macrophages and neurons after an in vivo LPS challenge compared to saline controls. Overall, our study emphasizes the role of inflammatory processes in the PNS that may be involved in sickness-behavior-associated hyperalgesia induced by systemic LPS treatment. Moreover, we present DRG primary cultures as tools to study inflammatory processes on a cellular level, not only in vitro but also ex vivo.
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Gilbertson-White, Stephanie, Nicole Bohr, and Karen E. Wickersham. "Conducting Biobehavioral Research in Patients With Advanced Cancer: Recruitment Challenges and Solutions." Biological Research For Nursing 19, no. 5 (May 16, 2017): 481–90. http://dx.doi.org/10.1177/1099800417709529.
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Despite significant advances in cancer treatment and symptom management interventions over the last decade, patients continue to struggle with cancer-related symptoms. Adequate baseline and longitudinal data are crucial for designing interventions to improve patient quality of life and reduce symptom burden; however, recruitment of patients with advanced cancer in longitudinal research is difficult. Our purpose is to describe challenges and solutions to recruitment of patients with advanced cancer in two biobehavioral research studies examining cancer-related symptoms. Study 1: Symptom data and peripheral blood for markers of inflammation were collected from newly diagnosed patients receiving chemotherapy on the first day of therapy and every 3–4 weeks for up to 6 months. Study 2: Symptom data, blood, and skin biopsies were collected from cancer patients taking epidermal growth factor receptor inhibitors at specific time points over 4 months. Screening and recruitment results for both studies are summarized. Timing informed consent with baseline data collection prior to treatment initiation was a significant recruitment challenge for both the studies. Possible solutions include tailoring recruitment to fit clinic needs, increasing research staff availability during clinic hours, and adding recruitment sites. Identifying solutions to these challenges will permit the conduct of studies that may lead to identification of factors contributing to variability in symptoms and development of tailored patient interventions for patients with advanced cancer.
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Hofstetter, Amelia R., William Van Bonn, and Randy E. Sacco. "Immunomediator expression profiling in two beluga whale (Delphinapterus leucas) clinical cases." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 59.6. http://dx.doi.org/10.4049/jimmunol.200.supp.59.6.
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Abstract Cytokines and other immunomediators can be biomarkers of inflammation. Quantitative real-time PCR (qPCR) has been used to examine cytokine gene expression in beluga whale (Delphinapterus leucas) peripheral blood mononuclear cells (PBMC). Thus, qPCR-based immunomediator assays could supplement clinical data from routine blood draws, revealing altered immune status. We compared immunomediator expression between beluga whales facing immune challenges and healthy companions at two aquaria. In both case studies, mitogens stimulated increased IL-1β, Cox2 and TNF-α message in PBMC from the abnormal whale over the control, but decreased IL-10 mRNA. This supports further elucidation of beluga PBMC immunomediator profiles for use as immune biomarkers.
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Pham, Grace, and Keisa Mathis. "Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus." Brain Sciences 8, no. 10 (October 4, 2018): 184. http://dx.doi.org/10.3390/brainsci8100184.
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Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-α were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation.
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Kustrimovic, Natasa, Franca Marino, and Marco Cosentino. "Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease." Current Medicinal Chemistry 26, no. 20 (September 13, 2019): 3719–53. http://dx.doi.org/10.2174/0929867325666181009161048.
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:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.
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Molfino, Alessio, Gianfranco Gioia, Filippo Rossi Fanelli, and Alessandro Laviano. "Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia." Mediators of Inflammation 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/801685.
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Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.
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Wils, Pauline, Bénédicte Caron, Ferdinando D’Amico, Silvio Danese, and Laurent Peyrin-Biroulet. "Abdominal Pain in Inflammatory Bowel Diseases: A Clinical Challenge." Journal of Clinical Medicine 11, no. 15 (July 22, 2022): 4269. http://dx.doi.org/10.3390/jcm11154269.
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Up to 60% of inflammatory bowel disease (IBD) patients experience abdominal pain in their lifetime regardless of disease activity. Pain negatively affects different areas of daily life and particularly impacts the quality of life of IBD patients. This review provides a comprehensive overview of the multifactorial etiology implicated in the chronic abdominal pain of IBD patients including peripheral sensitization by inflammation, coexistent irritable bowel syndrome, visceral hypersensitivity, alteration of the brain–gut axis, and the multiple factors contributing to pain persistence. Despite the optimal management of intestinal inflammation, chronic abdominal pain can persist, and pharmacological and non-pharmacological approaches are necessary. Integrating psychological support in care models in IBD could decrease disease burden and health care costs. Consequently, a multidisciplinary approach similar to that used for other chronic pain conditions should be recommended.
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Qin, Xuebin, Fengming Liu, Zhongnan Qin, and Jay Rappaport. "Characterization of renal macrophage (RM) fate, dynamics, and niches: embryonic RMs are more sensitive to immune challenges than bone marrow-derived RMs." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 149.5. http://dx.doi.org/10.4049/jimmunol.204.supp.149.5.
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Abstract Renal macrophages (RMs) participate in tissue homeostasis, inflammation, and repair. RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions, and metabolic states of the two RM populations remain unclear. Answering these questions will advance our understanding of the pathophysiological functions of tissue macrophages, in general, and RMs, in particular. To begin to address these important questions, we systematically investigated and functionally characterized RMs at different ages by conditionally labeling and ablating RM populations in several lines of transgenic mice. Here, we demonstrate: 1) RMs expand and mature in parallel with renal growth after birth; 2) RMs are mainly derived from fetal liver monocytes before birth, and self-maintain through adulthood with an approximately 40% contribution from peripheral monocytes; 3) After the RMs niche is emptied, peripheral monocytes rapidly differentiate into BMRMs, which preserve longevity; 4) The CX3CR1/CX3CL1 axis provides RMs niche signaling essential for the maintenance and regeneration of both EMRMs and BMRMs; 5) EMRMs have a higher capacity for scavenging immune complexes and are more sensitive to immune challenge than BMRMs; and 6) Differences in the glycolytic capacities of EMRMs and BMRMs correlate with distinct intrinsic functions and the response to immune challenge of the two RM populations.
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Mallesh, Shilpashree, Reiner Schneider, Bianca Schneiker, Mariola Lysson, Patrik Efferz, Eugene Lin, Wouter de Jonge, and Sven Wehner. "Sympathetic Denervation Alters the Inflammatory Response of Resident Muscularis Macrophages upon Surgical Trauma and Ameliorates Postoperative Ileus in Mice." International Journal of Molecular Sciences 22, no. 13 (June 26, 2021): 6872. http://dx.doi.org/10.3390/ijms22136872.
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Interactions between the peripheral nervous system and resident macrophages (MMs) modulate intestinal homeostatic functions. Activation of β2-adrenergic receptors on MMs has been shown to reduce bacterial challenges. These MMs are also crucial for the development of bowel inflammation in postoperative ileus (POI), an iatrogenic, noninfectious inflammation-based motility disorder. However, the role of the sympathetic nervous system (SNS) in the immune modulation of these MMs during POI or other noninfectious diseases is largely unknown. By employing 6-OHDA-induced denervation, we investigated the changes in the muscularis externa by RNA-seq, quantitative PCR, and flow cytometry. Further, we performed transcriptional phenotyping of sorted CX3CR1+ MMs and ex vivo LPS/M-CSF stimulation on these MMs. By combining denervation with a mouse POI model, we explored distinct changes on CX3CR1+ MMs as well as in the muscularis externa and their functional outcome during POI. Our results identify SNS as an important mediator in noninfectious postoperative inflammation. Upon denervation, MMs anti-inflammatory genes were reduced, and the muscularis externa profile is shaped toward a proinflammatory status. Further, denervation reduced MMs anti-inflammatory genes also in the early phase of POI. Finally, reduced leukocyte infiltration into the muscularis led to a quicker recovery of bowel motility in the late phase of POI.
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Karateev, A. E., D. E. Karateev, and O. S. Davydov. "PAIN AND INFLAMMATION. PART 1. PATHOGENETIC ASPECTS." Rheumatology Science and Practice 54, no. 6 (January 18, 2017): 693–704. http://dx.doi.org/10.14412/1995-4484-2016-693-704.
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The relief of suffering, which is associated with a rapid and complete elimination of painful sensations, is the most important challenge facing physicians of many specialties. It is obvious that it can be solved only when you understand clearly the processes governing the development and chronization of pain. Inflammation, a universal adaptive mechanism that always accompanies damage to living tissues, plays a key role. Part 1 of this review considers the main stages of development of an inflammatory response, beginning with primary damage accompanied by the release of molecules acting as an alarm and ending with the deployment of a complete picture of the inflammatory response with the involvement of many cell elements and the overexpression of cytokines and proinflammatory mediators. The biological basis of the peripheral and central nociceptive sensitization phenomenon that is rigidly associated with inflammation is presented. Particular emphasis is placed on the possible natural completion of the inflammatory response, on the adaptive mechanisms regulating this process and on the reasons that prevent this and determines inflammation chronization.
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Qian, Yun, Yuan Cheng, Jiangyu Cai, Xiaotian Zhao, Yuanming Ouyang, Wei-En Yuan, and Cunyi Fan. "Advances in electrical and magnetic stimulation on nerve regeneration." Regenerative Medicine 14, no. 10 (October 2019): 969–79. http://dx.doi.org/10.2217/rme-2018-0079.
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Central and peripheral nerve injuries pose a great threat to people. Complications such as inflammation, muscle atrophy, traumatic neuromas and delayed reinnervation can bring huge challenges to clinical practices and barriers to complete nerve regrowth. Physical interventions such as electrical and magnetic stimulation show satisfactory results with varying parameters for acute and chronic nerve damages. The biological basis of electrical and magnetic stimulation mainly relies on protein synthesis, ion channel regulation and growth factor secretion. This review focuses on the various paradigms used in different models of electrical and magnetic stimulation and their regenerative potentials and underlying mechanisms in nerve injuries. The combination of physical stimulation and conductive biomaterial scaffolds displays an infinite potentiality in translational application in nerve regeneration.
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Herman, Andrzej P., Dorota Tomaszewska-Zaremba, Marta Kowalewska, Aleksandra Szczepkowska, Małgorzata Oleszkiewicz, Agata Krawczyńska, Maciej Wójcik, Hanna Antushevich, and Janina Skipor. "Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation." Mediators of Inflammation 2018 (October 9, 2018): 1–9. http://dx.doi.org/10.1155/2018/9150207.
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The study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin—lipopolysaccharide (LPS; 400 ng/kg)—attenuates the synthesis of proinflammatory cytokines in the ovine preoptic area (POA), the hypothalamic structure playing an essential role in the control of the reproduction process, and in the choroid plexus (CP), a multifunctional organ sited at the interface between the blood and cerebrospinal fluid in the ewe. Neostigmine suppressed (p<0.05) LPS-stimulated synthesis of cytokines such as interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF) α in the POA, and this effect was similar to that induced by the treatment with systemic AChE inhibitor—donepezil (2.5 mg/animal). On the other hand, both AChE inhibitors did not influence the gene expression of these cytokines and their corresponding receptors in the CP. It was found that this structure seems to not express the neuronal acetylcholine (ACh) receptor subunit alpha-7, required for anti-inflammatory action of ACh. The mechanism of action involves inhibition of the proinflammatory cytokine synthesis on the periphery as well as inhibition of their de novo synthesis rather in brain microvessels and not in the CP. In conclusion, it is suggested that the AChE inhibitors incapable of reaching brain parenchyma might be used in the treatment of neuroinflammatory processes induced by peripheral inflammation.
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Bever, Savannah R., Xiaoyu Liu, Ning Quan, and Leah M. Pyter. "Euflammation Attenuates Central and Peripheral Inflammation and Cognitive Consequences of an Immune Challenge after Tumor Development." Neuroimmunomodulation 24, no. 2 (2017): 74–86. http://dx.doi.org/10.1159/000479184.
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Pyter, M., S. R. Bever, X. Liu, and N. Quan. "Euflammation attenuates central and peripheral inflammation and cognitive consequences of an immune challenge after tumor development." Brain, Behavior, and Immunity 66 (November 2017): e16. http://dx.doi.org/10.1016/j.bbi.2017.07.067.
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Kentner, A. C., and Q. J. Pittman. "Minireview: Early-Life Programming by Inflammation of the Neuroendocrine System." Endocrinology 151, no. 10 (July 28, 2010): 4602–6. http://dx.doi.org/10.1210/en.2010-0583.
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Acute inflammation results in alterations in both peripheral and central nervous system cytokine levels that together can exert transient but profound alterations in neuroendocrine function. This has been particularly well studied with respect to the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal axes. There is now evidence, particularly in rodents, that an inflammation in the neonatal period can have long-term, sex-specific effects on these neuroendocrine axes that persist into adulthood. There are critical time periods for the establishment of these long-term programming effects, and in adulthood they may be revealed either as alterations in basal functioning or in altered responses to a subsequent inflammatory challenge. These studies highlight the importance of early environmental exposure to pathogens in sculpting adult physiology and behavior.
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Lim, Dae Hyun, Jae Youn Cho, Dae Jin Song, Sang Yeub Lee, Marina Miller, and David H. Broide. "PI3Kγ-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling." American Journal of Physiology-Lung Cellular and Molecular Physiology 296, no. 2 (February 2009): L210—L219. http://dx.doi.org/10.1152/ajplung.90275.2008.
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In this study, we have examined the role of phosphoinositide 3 kinase γ (PI3Kγ), a class Ib PI3K, in contributing to airway remodeling utilizing PI3Kγ-deficient mice exposed to chronic allergen challenge. Wild-type (WT) mice sensitized to ovalbumin (OVA) and chronically challenged with OVA for 1 mo developed significantly increased levels of eosinophilic inflammation and airway remodeling. In contrast, PI3Kγ-deficient mice challenged with OVA had significantly reduced numbers of bronchoalveolar lavage and peribronchial eosinophils compared with WT mice. There was no significant difference in the number of bone marrow or circulating peripheral blood eosinophils when comparing WT mice and PI3Kγ-deficient mice, suggesting that trafficking of eosinophils into the lung was reduced in PI3Kγ-deficient mice. PI3Kγ-deficient and WT mice had similar levels of IL-5 and eotaxin-1. The reduced eosinophil recruitment to the airway in PI3Kγ-deficient mice challenged with OVA was associated with significantly reduced numbers of TGF-β1+ peribronchial cells, reduced numbers of pSmad 2/3+ airway epithelial cells, and pSmad 2/3+ peribronchial cells, as well as significantly reduced levels of peribronchial fibrosis (quantitated by trichrome staining and image analysis as well as by lung collagen levels). In addition, the area of peribronchial α-smooth muscle staining was significantly reduced in PI3Kγ-deficient compared with WT mice. Overall, this study demonstrates an important role for PI3Kγ in mediating allergen-induced eosinophilic airway inflammation and airway remodeling, suggesting that PI3Kγ may be a novel therapeutic target in asthma.
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Beijer, Lena, Jörgen Thorn, and Ragnar Rylander. "Effects after inhalation of (1 → 3)-β-D-glucan and relation to mould exposure in the home." Mediators of Inflammation 11, no. 3 (2002): 149–53. http://dx.doi.org/10.1080/09622935020138181.
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Background: Damp conditions indoors favour the growth of microorganisms, and these contain several agents that may cause inflammation when inhaled. Moulds contain a polyglucose in their cell wall, defined as (1→3)-β-D-glucan, exhibiting effects on inflammatory cells.Aim: The aim of the present study was to evaluate whether an inhalation challenge to purified (1→3)-β-D-glucan (grifolan) in humans could induce effects on inflammatory markers in blood, and to evaluate whether the reactions were related to the home exposure to (1→3)-β-D-glucan.Methods: Seventeen subjects in homes with high levels of airborne (1→3)-β-D-glucan (G-high) and 18 subjects in homes with low levels of (1→3)-β-D-glucan (G-low) underwent two randomised, double-blind inhalation challenges, one to (1→3)-β-D-glucan suspended in saline and one to saline alone. A blood sample was taken before and after the challenges, and differential cell count, granulocyte enzymes in serum and the secretion of cytokines from peripheral blood mononuclear cells (PBMC) were measured.Results: Inhalation challenge with (1→3)-β-D-glucan induced a decrease in the secretion of tumour necrosis factor α from endotoxin-stimulated PBMC in the G-high group as well as in the G-low group. In the G-high group, the inhalation of (1→3)-β-D-glucan induced an increase in blood lymphocytes that was significantly different from the saline-induced effect.Conclusions: The results suggest that an inhalation challenge to (1→3)-β-D-glucan has an effect on inflammatory cells and this effect may be related to a chronic exposure to moulds at home.
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Sahasrabudhe, Siddhee A., Marcia R. Terluk, Kyle D. Rudser, James C. Cloyd, and Reena V. Kartha. "Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease." International Journal of Molecular Sciences 23, no. 16 (August 16, 2022): 9189. http://dx.doi.org/10.3390/ijms23169189.
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The lack of reliable biomarkers is a significant challenge impeding progress in orphan drug development. For appropriate interpretation of intervention-based results or for evaluating candidate biomarkers, other things being equal, lower variability in biomarker measurement would be helpful. However, variability in rare disease biomarkers is often poorly understood. Type 1 Gaucher disease (GD1) is one such rare lysosomal storage disorder. Oxidative stress and inflammation have been linked to the pathophysiology of GD1 and validated measures of these processes can provide predictive value for treatment success or disease progression. This study was undertaken to investigate and compare the extent of longitudinal biological variation over a three-month period for various blood-based oxidative stress and inflammation markers in participants with GD1 on stable standard-of-care therapy (N = 13), treatment-naïve participants with GD1 (N = 5), and in age- and gender-matched healthy volunteers (N = 18). We utilized Bland–Altman plots for visual comparison of the biological variability among the three measurements. We also report group-wise means and the percentage of coefficient of variation (%CV) for 15 biomarkers. Qualitatively, we show specific markers (IL-1Ra, IL-8, and MIP-1b) to be consistently altered in GD1, irrespective of therapy status, highlighting the need for adjunctive therapies that can target and modulate these biomarkers. This information can help guide the selection of candidate biomarkers for future intervention-based studies in GD1 patients.
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Fliers, Eric, Andries Kalsbeek, and Anita Boelen. "MECHANISMS IN ENDOCRINOLOGY: Beyond the fixed setpoint of the hypothalamus–pituitary–thyroid axis." European Journal of Endocrinology 171, no. 5 (November 2014): R197—R208. http://dx.doi.org/10.1530/eje-14-0285.
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The hypothalamus–pituitary–thyroid (HPT) axis represents a classical example of an endocrine feedback loop. This review discusses dynamic changes in HPT axis setpoint regulation, identifying their molecular and cellular determinants, and speculates about their functional role. Hypothalamic thyrotropin-releasing hormone neurons were identified as key components of thyroid hormone (TH) setpoint regulation already in the 1980s, and this was followed by the demonstration of a pivotal role for the thyroid hormone receptor beta in negative feedback of TH on the hypothalamic and pituitary level. Gradually, the concept emerged of the HPT axis setpoint as a fixed entity, aiming at a particular TH serum concentration. However, TH serum concentrations appear to be variable and highly responsive to physiological and pathophysiological environmental factors, including the availability or absence of food, inflammation and clock time. During food deprivation and inflammation, TH serum concentrations decrease without a concomitant rise in serum TSH, reflecting a deviation from negative feedback regulation in the HPT axis. Surprisingly, TH action in peripheral organs in these conditions cannot be simply predicted by decreased serum TH concentrations. Instead, diverse environmental stimuli have differential effects on local TH metabolism, e.g. in liver and muscle, occurring quite independently from decreased TH serum concentrations. The net effect of these differential local changes is probably a major determinant of TH action at the tissue level. In sum, hypothalamic HPT axis setpoint regulation as well as TH metabolism at the peripheral organ level is flexible and dynamic, and may adapt the organism in an optimal way to a range of environmental challenges.
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Menzel, Alain, Hanen Samouda, Francois Dohet, Suva Loap, Mohammed S. Ellulu, and Torsten Bohn. "Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice—Which to Use Regarding Disease Outcomes?" Antioxidants 10, no. 3 (March 9, 2021): 414. http://dx.doi.org/10.3390/antiox10030414.
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Many chronic conditions such as cancer, chronic obstructive pulmonary disease, type-2 diabetes, obesity, peripheral/coronary artery disease and auto-immune diseases are associated with low-grade inflammation. Closely related to inflammation is oxidative stress (OS), which can be either causal or secondary to inflammation. While a low level of OS is physiological, chronically increased OS is deleterious. Therefore, valid biomarkers of these signalling pathways may enable detection and following progression of OS/inflammation as well as to evaluate treatment efficacy. Such biomarkers should be stable and obtainable through non-invasive methods and their determination should be affordable and easy. The most frequently used inflammatory markers include acute-phase proteins, essentially CRP, serum amyloid A, fibrinogen and procalcitonin, and cytokines, predominantly TNFα, interleukins 1β, 6, 8, 10 and 12 and their receptors and IFNγ. Some cytokines appear to be disease-specific. Conversely, OS—being ubiquitous—and its biomarkers appear less disease or tissue-specific. These include lipid peroxidation products, e.g., F2-isoprostanes and malondialdehyde, DNA breakdown products (e.g., 8-OH-dG), protein adducts (e.g., carbonylated proteins), or antioxidant status. More novel markers include also –omics related ones, as well as non-invasive, questionnaire-based measures, such as the dietary inflammatory-index (DII), but their link to biological responses may be variable. Nevertheless, many of these markers have been clearly related to a number of diseases. However, their use in clinical practice is often limited, due to lacking analytical or clinical validation, or technical challenges. In this review, we strive to highlight frequently employed and useful markers of inflammation-related OS, including novel promising markers.
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Williams, Isabelle, Sumeet Pandey, Wolfram Haller, Hien Quoc Huynh, Alicia Chan, Gesche Düeker, Ruth Bettels, et al. "Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C." Wellcome Open Research 7 (January 11, 2022): 11. http://dx.doi.org/10.12688/wellcomeopenres.16986.1.
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Background: Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn’s Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with neurological deterioration, liver damage and respiratory infections. Some NPC1 patients develop severe Crohn’s disease. Our objective was to investigate the safety and effectiveness of anti-TNF in NPC1 patients with Crohn’s disease. Methods: Retrospective data on phenotype and therapy response were collected in 2019-2020 for the time period 2014 to 2020 from patients in the UK, France, Germany and Canada with genetically confirmed NPC1 defects and intestinal inflammation. We investigated TNF secretion in peripheral blood mononuclear cells treated with NPC1 inhibitor in response to bacterial stimuli. Results: NPC1 inhibitor treated peripheral blood mononuclear cells (PBMCs) show significantly increased TNF production after lipopolysaccharide or bacterial challenge providing a rationale for anti-TNF therapy. We identified 4 NPC1 patients with Crohn’s disease (CD)-like intestinal inflammation treated using anti-TNF therapy (mean age of onset 8.1 years, mean treatment length 27.75 months, overall treatment period 9.25 patient years). Anti-TNF therapy was associated with reduced gastrointestinal symptoms with no apparent adverse neurological events. Therapy improved intestinal inflammation in 4 patients. Conclusions: Anti-TNF therapy appears safe in patients with NPC1 and is an effective treatment strategy for the management of intestinal inflammation in these patients.
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Stanzani, Agnese, Anna Sansone, Cinzia Brenna, Vito Antonio Baldassarro, Giuseppe Alastra, Luca Lorenzini, Chryssostomos Chatgilialoglu, et al. "Erythrocyte Plasma Membrane Lipid Composition Mirrors That of Neurons and Glial Cells in Murine Experimental In Vitro and In Vivo Inflammation." Cells 12, no. 4 (February 9, 2023): 561. http://dx.doi.org/10.3390/cells12040561.
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Lipid membrane turnover and myelin repair play a central role in diseases and lesions of the central nervous system (CNS). The aim of the present study was to analyze lipid composition changes due to inflammatory conditions. We measured the fatty acid (FA) composition in erythrocytes (RBCs) and spinal cord tissue (gas chromatography) derived from mice affected by experimental allergic encephalomyelitis (EAE) in acute and remission phases; cholesterol membrane content (Filipin) and GM1 membrane assembly (CT-B) in EAE mouse RBCs, and in cultured neurons, oligodendroglial cells and macrophages exposed to inflammatory challenges. During the EAE acute phase, the RBC membrane showed a reduction in polyunsaturated FAs (PUFAs) and an increase in saturated FAs (SFAs) and the omega-6/omega-3 ratios, followed by a restoration to control levels in the remission phase in parallel with an increase in monounsaturated fatty acid residues. A decrease in PUFAs was also shown in the spinal cord. CT-B staining decreased and Filipin staining increased in RBCs during acute EAE, as well as in cultured macrophages, neurons and oligodendrocyte precursor cells exposed to inflammatory challenges. This regulation in lipid content suggests an increased cell membrane rigidity during the inflammatory phase of EAE and supports the investigation of peripheral cell membrane lipids as possible biomarkers for CNS lipid membrane concentration and assembly.
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Diez-Ahedo, Ruth, Xabier Mendibil, Mari Carmen Márquez-Posadas, Iban Quintana, Francisco González, Francisco Javier Rodríguez, Leyla Zilic, et al. "UV-Casting on Methacrylated PCL for the Production of a Peripheral Nerve Implant Containing an Array of Porous Aligned Microchannels." Polymers 12, no. 4 (April 22, 2020): 971. http://dx.doi.org/10.3390/polym12040971.
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Peripheral nerves are basic communication structures guiding motor and sensory information from the central nervous system to receptor units. Severed peripheral nerve injuries represent a large clinical problem with relevant challenges to successful synthetic nerve repair scaffolds as substitutes to autologous nerve grafting. Numerous studies reported the use of hollow tubes made of synthetic polymers sutured between severed nerve stumps to promote nerve regeneration while providing protection for external factors, such as scar tissue formation and inflammation. Few approaches have described the potential use of a lumen structure comprised of microchannels or microfibers to provide axon growth avoiding misdirection and fostering proper healing. Here, we report the use of a 3D porous microchannel-based structure made of a photocurable methacrylated polycaprolactone, whose mechanical properties are comparable to native nerves. The neuro-regenerative properties of the polymer were assessed in vitro, prior to the implantation of the 3D porous structure, in a 6-mm rat sciatic nerve gap injury. The manufactured implants were biocompatible and able to be resorbed by the host’s body at a suitable rate, allowing the complete healing of the nerve. The innovative design of the highly porous structure with the axon guiding microchannels, along with the observation of myelinated axons and Schwann cells in the in vivo tests, led to a significant progress towards the standardized use of synthetic 3D multichannel-based structures in peripheral nerve surgery.
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Khare, Anupriya, Nandini Krishnamoorthy, Mahesh Raundhal, Christina Morse, Prabir Ray, and Anuradha Ray. "Peroxisome proliferator-activated receptor-gamma in CD11c+ lung dendritic cells programs peripheral CD4+ T cells for Foxp3 induction during airway tolerance. (P6001)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 120.1. http://dx.doi.org/10.4049/jimmunol.190.supp.120.1.
Full textAbstract:
Abstract Peroxisome proliferator-activated receptor-gamma (PPARγ) is a widely expressed molecular regulator with anti-inflammatory functions. However, whether it has an anti-inflammatory role in dendritic cells (DCs) that influence the Treg/Teffector balance has not been experimentally addressed. In this study, we investigated the role of PPARγ in DCs regulating the delicate balance between tolerance versus inflammation in the periphery using a model of airway induced tolerance by inhaled allergen. Using mice with selective deletion of PPARγ in CD11c+ cells, we observed that PPARγ expression in CD11chi lung DCs is essential for de novo Foxp3 expression in CD4+ T cells. We demonstrate that PPARγ plays a crucial role in enhancing aldh1a2 expression in lung CD103+ DCs under tolerogenic conditions with significantly less expression of the enzyme in these cells when mice are immunized for airway inflammation. When tolerized CD11ccre/+ PPARγfl/fl mice were antigen-challenged, a complete loss of immune tolerance with increased neutrophil-dominated airway inflammation was observed. Taken together, our study identifies PPARγ as a central regulator in DC-mediated programming of Foxp3 expression in naive CD4+ T cells dictating tolerance versus inflammation upon antigen provocation.
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Pena, Olga, Disha Raj, Jelena Pistolic, Christopher Fjell, and Robert Hancock. "Endotoxin Tolerance represents a state of alternative polarization in mononuclear cells (142.4)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 142.4. http://dx.doi.org/10.4049/jimmunol.184.supp.142.4.
Full textAbstract:
Abstract Classical (M1) and alternative (M2) polarization of mononuclear cells such as monocyte and macrophages, mainly occurs as a response to micro-environmental challenges such as the incursion of a pathogen. Lipopolysaccharide, also known as endotoxin (LPS), is a potent inducer of inflammation and M1 polarization. LPS can also generate an effect in mononuclear cells known as endotoxin tolerance, defined as the reduced capacity of the cell to respond to LPS activation following a first exposure to this stimulus. Using systems biology approaches in peripheral blood mononuclear cells and monocyte derived macrophages, we identified that endotoxin tolerance is characterized by a similar state of alternative polarization, featuring expression of genes and proteins critical for the development of key M2 functions, including reduced production of pro-inflammatory mediators, expression of genes involved in phagocytosis as well as tissue remodeling. Moreover, expression of different methallothionein gene isoforms, known for their role in the control of oxidative stress and immunomodulation was also found consistently up-regulated during endotoxin tolerance. These results favor the hypothesis that, after an initial inflammatory stimulus, mononuclear cells undergo an alternative polarization most probably to control and balance prospective hyper-inflammation.
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Bach Knudsen, Knud, Helle Lærke, Mette Hedemann, Tina Nielsen, Anne Ingerslev, Ditte Gundelund Nielsen, Peter Theil, et al. "Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation." Nutrients 10, no. 10 (October 13, 2018): 1499. http://dx.doi.org/10.3390/nu10101499.
Full textAbstract:
A major challenge in affluent societies is the increase in disorders related to gut and metabolic health. Chronic over nutrition by unhealthy foods high in energy, fat, and sugar, and low in dietary fibre is a key environmental factor responsible for this development, which may cause local and systemic inflammation. A low intake of dietary fibre is a limiting factor for maintaining a viable and diverse microbiota and production of short-chain fatty acids in the gut. A suppressed production of butyrate is crucial, as this short-chain fatty acid (SCFA) can play a key role not only in colonic health and function but also at the systemic level. At both sites, the mode of action is through mediation of signalling pathways involving nuclear NF-κB and inhibition of histone deacetylase. The intake and composition of dietary fibre modulate production of butyrate in the large intestine. While butyrate production is easily adjustable it is more variable how it influences gut barrier function and inflammatory markers in the gut and periphery. The effect of butyrate seems generally to be more consistent and positive on inflammatory markers related to the gut than on inflammatory markers in the peripheral tissue. This discrepancy may be explained by differences in butyrate concentrations in the gut compared with the much lower concentration at more remote sites.
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Huang, C. Chris, Karen E. Duffy, Lani R. San Mateo, Bernard Y. Amegadzie, Robert T. Sarisky, and M. Lamine Mbow. "A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells." Physiological Genomics 26, no. 2 (July 2006): 125–33. http://dx.doi.org/10.1152/physiolgenomics.00002.2006.
Full textAbstract:
To gain global pathway perspective of ex vivo viral infection models using human peripheral blood mononuclear cells (PBMCs), we conducted expression analysis on PBMCs of healthy donors. RNA samples were collected at 3 and 24 h after PBMCs were challenged with the Toll-like receptor-3 (TLR3) agonist polyinosinic acid-polycytidylic acid [poly(I:C)] and analyzed by internally developed cDNA microarrays and TaqMan PCR. Our results demonstrate that poly(I:C) challenge can elicit certain gene expression changes, similar to acute viral infection. Hierarchical clustering revealed distinct immediate early, early-to-late, and late gene regulation patterns. The early responses were innate immune responses that involve TLR3, the NF-κB-dependent pathway, and the IFN-stimulated pathway, whereas the late responses were mostly cell-mediated immune response that involve activation of cell adhesion, cell mobility, and phagocytosis. Overall, our results expanded the utilities of this ex vivo model, which could be used to screen molecules that can modulate viral stress-induced inflammation, in particular those mediated via TLRs.
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Guo, junfei, Hooman Derakshani, Ilkyu Yoon, Khafipour Khafipour, and Jan C. Plaizier. "405 Effect of Subacute Ruminal Acidosis (SARA) and Saccharomyces cerevisiae fermentation products on inflammatory responses of dairy cows." Journal of Animal Science 97, Supplement_3 (December 2019): 164. http://dx.doi.org/10.1093/jas/skz258.337.
Full textAbstract:
Abstract Feeding high-grain diets to dairy cows increases concentrations of acute phase proteins in peripheral blood. This inflammatory response can be reduced by supplementation with Saccharomyces cerevisiae fermentation products (SCFP). It is not clear which cytokines drive this inflammatory response, which organs are inflamed, and how these processes are affected by SCFP. The objectives of this study were to investigate if grain-induced SARA increases the concentrations of the cytokines IL-1β in peripheral blood, and of the inflammatory marker myeloperoxidase (MPO) in rumen papillae of lactating dairy cows, and if these concentrations are affected by SCFP. Thirty-two lactating Holstein dairy cows were randomly assigned to four treatment groups (n = 8) that received a TMR (34.9 %DM NDF, 18.6 %DM starch) supplemented with 1) 140 g/d of ground corn (Control), 2) 126 g/d corn and 14 g/d of Diamond V Original XPCTM (XPC), 3) 121 g/d corn and 19 g/d Diamond V NutriTek® (NTL), and 4) 102 g/d corn and 38 g/d of Diamond V NutriTek® (NTH). SARA challenges were conducted during wk 5 (SARA1) and 8 (SARA2) of lactation by replacing 20% of the base TMR with pellets containing 50% barley and 50% wheat. Blood samples were taken weekly between wk 4 (preSARA1) and wk 9 (postSARA2) for the analysis of IL-1β. Rumen papillae samples were taken during wk 3 (preSARA1) and wk 9 (postSARA2) for the measurement of MPO. SCFP treatment did not affect the concentrations of IL-1β, but the SARA challenges increased this concentration moderately from 9.0 to 12.3 pg/mL (P < 0.05). The concentration of MPO did not differ between preSARA1 and postSARA2, and these concentrations were not affected by SCFP. Results suggest that IL-1β may drive the acute phase response during the SARA challenges, and that these challenges did not cause inflammation of rumen papillae.