Critical Involvement of Cytokines and Chemokines in the Pathogenesis of Rheumatoid Vasculitis

2008 ◽  
Vol 1 ◽  
pp. CMAMD.S534
Author(s):  
Tsuyoshi Kasama ◽  
Takeo Isozaki ◽  
Kuninobu Wakabayashi ◽  
Tsuyoshi Odai ◽  
Mizuho Matsunawa
Keyword(s):  
Rheumatoid Arthritis ◽  
Adhesion Molecules ◽  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
Inflammatory Responses ◽  
Rheumatoid Vasculitis ◽  
Cytokines And Chemokines ◽  
Eye Symptoms ◽  
Arthritis Rheumatoid

Vasculitis in rheumatoid arthritis (rheumatoid vasculitis) has a heterogeneous clinical presentation that includes skin disorders, neuropathy, eye symptoms and systemic inflammation. The molecular mechanisms underlying rheumatoid vasculitis are not fully understood; however, the importance of a chronic imbalance of the cytokines and chemokines involved in orchestrating inflammatory responses is well established in patients with rheumatoid arthritis, and similar dysregulation of these mediators has been suggested to occur in patients with rheumatoid vasculitis. In the present review, we discuss the involvement of cytokines and chemokines in the pathogenesis of rheumatoid vasculitis and evaluate their utility as laboratory parameters of active vasculitic disease. Also the involvement of adhesion molecules is discussed.

scholarly journals CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Sheng-Mou Hou ◽  
Po-Chun Chen ◽  
Chieh-Mo Lin ◽  
Mei-Ling Fang ◽  
Miao-Ching Chi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Chemical Inhibitors ◽  
Shrna Plasmid ◽  
Signal Cascades

Abstract Background Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well characterized in RA progression, but less so in OA pathogenesis. Methods The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze the expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs, and shRNAs. Results Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf, and MAPKs were found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs. Conclusions Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.

scholarly journals CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK and AP-1 pathway

2020 ◽  
Author(s):  
Sheng-Mou Hou ◽  
PoChun Chen ◽  
Chieh-Mo Lin ◽  
Mei-Ling Fang ◽  
Miao-Ching Chi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Chemical Inhibitors ◽  
Shrna Plasmid ◽  
Signal Cascades

Abstract Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well-characterized in RA progression, but less so in OA pathogenesis.Methods: The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs and shRNAs.Results: Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf and MAPKs was found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs.Conclusions: Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.

scholarly journals New insight into the rheumatoid vasculitis

2015 ◽  
Vol 53 (2) ◽  
pp. 128-132 ◽  
Author(s):  
M. Cojocaru ◽  
Inimioara Mihaela Cojocaru ◽  
B. Chicoş
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Vessels ◽  
Typical Feature ◽  
Skin Condition ◽  
Vascular Lesions ◽  
Unusual Complication ◽  
Rheumatoid Vasculitis ◽  
Internal Organs ◽  
Eye Symptoms ◽  
Insight Into

Abstract Vasculitis in rheumatoid arthritis (rheumatoid vasculitis, RV) has a heterogeneous clinical presentation that includes skin disorders, neuropathy, eye symptoms and systemic inflammation. Rheumatoid vasculitis is an unusual complication of longstanding, severe rheumatoid arthritis (RA). While RA affects the body’s joints, vasculitis is a condition in which blood vessels become inflamed. Rheumatoid vasculitis occurs in approximately 2 to 5% of patients who have RA. The blood vessels most often involved are arteries that bring blood to the skin, nerves, and internal organs. Veins can also be involved. Rheumatoid vasculitis is skin condition that is a typical feature of RA, presenting as peripheral vascular lesions that are localized (purpura, cutaneous ulceration, and gangrene of the distal parts of the extremities). The cause of RV is unknown, but given the prominence of immune components and the pathologic changes in involved blood vessels, an autoimmune process is suggested. Compared to other forms of vasculitis, there has been relatively little research in recent years on the specific entity of RV. There is some evidence that the incidence of RV has decreased over the past several decades, perhaps because of a better treatment of the underlying RA. In the present review, we discuss the clinical features, laboratory tests, the pathogenesis of RV.

scholarly journals Novel insights into the neuroendocrine control of inflammation: the role of GR and PARP1

2014 ◽  
Vol 3 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
Fernando Aprile-Garcia ◽  
María Antunica-Noguerol ◽  
Maia Ludmila Budziñski ◽  
Ana C Liberman ◽  
Eduardo Arzt
Keyword(s):  
Inflammatory Mediators ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Activator Protein 1 ◽  
Post Translational Modification ◽  
Cytokines And Chemokines ◽  
Inflammatory Processes ◽  
Neuroendocrine Axis

Inflammatory responses are elicited after injury, involving release of inflammatory mediators that ultimately lead, at the molecular level, to the activation of specific transcription factors (TFs; mainly activator protein 1 and nuclear factor-κB). These TFs propagate inflammation by inducing the expression of cytokines and chemokines. The neuroendocrine system has a determinant role in the maintenance of homeostasis, to avoid exacerbated inflammatory responses. Glucocorticoids (GCs) are the key neuroendocrine regulators of the inflammatory response. In this study, we describe the molecular mechanisms involved in the interplay between inflammatory cytokines, the neuroendocrine axis and GCs necessary for the control of inflammation. Targeting and modulation of the glucocorticoid receptor (GR) and its activity is a common therapeutic strategy to reduce pathological signaling. Poly (ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes the addition of PAR on target proteins, a post-translational modification termed PARylation. PARP1 has a central role in transcriptional regulation of inflammatory mediators, both in neuroendocrine tumors and in CNS cells. It is also involved in modulation of several nuclear receptors. Therefore, PARP1 and GR share common inflammatory pathways with antagonic roles in the control of inflammatory processes, which are crucial for the effective maintenance of homeostasis.

Chronic Tobacco Exposure by Smoking Develops Insulin Resistance

2020 ◽  
Vol 20 (6) ◽  
pp. 869-877
Author(s):  
Suchismita Mukharjee ◽  
Sarbashri Bank ◽  
Smarajit Maiti
Keyword(s):  
Insulin Resistance ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Antioxidant Defense System ◽  
Polymorphonuclear Neutrophils ◽  
Therapeutic Interventions ◽  
Occurrence Rate ◽  
Tobacco Exposure ◽  
Skeletal Muscle Insulin Resistance ◽  
Cytokines And Chemokines

Background and Objectives: The present review critically discusses the high occurrence rate, insulin resistance and type-2 diabetes in tobacco exposed individuals. Tobacco extracts and smoke contain a large number of toxic materials and a significant number of those are metabolic disintegrators. Discussion: Glucose and lipid homeostasis is severely impaired by this compound. Tobacco exposure contributes to adverse effects by impairing the physical, biochemical and molecular mechanisms in the tissues. The immunological components are damaged by tobacco with high production of proinflammatory cytokines (IL-6, TNF-∞) and augmentation of inflammatory responses. These events result in damages to cytoskeletal structures of different tissues. Degradation of matrix structure (by activation of different types of MMPs) results in the permanent damages to the tissues and their metabolic functions. Cellular antioxidant defense system mostly cannot or hardly nullify CS-induced ROS production that activates polymorphonuclear neutrophils (PMNs), which are a major source of cytokines and chemokines (TNFα, IL6, IL8, INFγ). Additive effects of these immediately promote the low energy-metabolism as well as inflammation. Oxidative stress, mitochondrial dysfunction, and inflammation contribute to the direct nicotine toxicity via nAChRs in diabetes. The investigator identified that skeletal muscle insulin-resistance occurs in smokers due to phosphorylation of insulin receptor substrate1 (IRS1) at Ser-636 position. Conclusion: Tobacco exposure initiates free radical related immunological impairment, DNA damage, and inflammation. So, the present analysis is of importance to figure out the mechanistic layout of tobacco-induced tissue damage and its possible therapeutic interventions.

scholarly journals CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK and AP-1 pathway

2020 ◽  
Author(s):  
Sheng-Mou Hou ◽  
PoChun Chen ◽  
Chieh-Mo Lin ◽  
Mei-Ling Fang ◽  
Miao-Ching Chi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Chemical Inhibitors ◽  
Shrna Plasmid ◽  
Signal Cascades

Abstract Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well-characterized in RA progression, but less so in OA pathogenesis. Methods: The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs and shRNAs. Results: Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf and MAPKs was found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs. Conclusions: Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.

scholarly journals CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK and AP-1 pathway

2020 ◽  
Author(s):  
PoChun Chen ◽  
Sheng-Mou Hou ◽  
Ju-Fang Liu
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Chemical Inhibitors ◽  
Shrna Plasmid ◽  
Signal Cascades

Abstract Background Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well-characterized in RA progression, but less so in OA pathogenesis. Methods The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs and shRNAs. Results Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf and MAPKs was found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs. Conclusions Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.

scholarly journals Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators

2021 ◽  
Author(s):  
Jinho Seo ◽  
Young Woo Nam ◽  
Seongmi Kim ◽  
Doo-Byoung Oh ◽  
Jaewhan Song
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Gene Knockout ◽  
Specific Inhibitor ◽  
Kinase Domain ◽  
Interacting Protein ◽  
Membrane Rupture ◽  
Cytokines And Chemokines

AbstractNecroptosis is a form of programmed necrosis that is mediated by various cytokines and pattern recognition receptors (PRRs). Cells dying by necroptosis show necrotic phenotypes, including swelling and membrane rupture, and release damage-associated molecular patterns (DAMPs), inflammatory cytokines, and chemokines, thereby mediating extreme inflammatory responses. Studies on gene knockout or necroptosis-specific inhibitor treatment in animal models have provided extensive evidence regarding the important roles of necroptosis in inflammatory diseases. The necroptosis signaling pathway is primarily modulated by activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates mixed-lineage kinase domain-like protein (MLKL), mediating MLKL oligomerization. In the necroptosis process, these proteins are fine-tuned by posttranslational regulation via phosphorylation, ubiquitination, glycosylation, and protein–protein interactions. Herein, we review recent findings on the molecular regulatory mechanisms of necroptosis.

scholarly journals Cytokines and Chemokines in Chikungunya Virus Infection: Protection or Induction of Pathology

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 415
Author(s):  
Chintana Chirathaworn ◽  
Jira Chansaenroj ◽  
Yong Poovorawan
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Chikungunya Virus ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Joint Inflammation ◽  
Chikv Infection ◽  
Chemokine Production ◽  
Persistent Symptoms ◽  
Cytokines And Chemokines

Chikungunya virus (CHIKV) infection has been commonly detected in tropical countries. The clinical manifestations of CHIKV infection are similar to those of rheumatoid arthritis. Outbreaks of CHIKV infection in Thailand have been reported, and the inductions of various cytokines and chemokines in CHIKV patients during those outbreaks have been shown. Although immune responses in CHIKV infection have been increasingly reported, the mechanisms associated with pathology induction are still not clearly understood. This review focuses on cytokine and chemokine production in CHIKV infection, in association with the severity of joint inflammation. Several cytokines and chemokines involved in the induction or regulation of inflammatory responses were shown to associate with the severe and persistent symptoms in CHIKV infection. Further studies on the difference in immune responses observed in an autoimmune disease, rheumatoid arthritis, infectious disease, and CHIKV infection, would provide additional insights useful for proper CHIKV therapy, especially in patients with severe joint pains.

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