Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis
Takanori Shouda,Takafumi Yoshida,Takafumi Yoshida,Toshikatsu Hanada,Toru Wakioka,Toru Wakioka,Masanobu Oishi,Kanta Miyoshi,Kanta Miyoshi,Setsuro Komiya,Ken-ichiro Kosai,Yasushi Hanakawa,Koji Hashimoto,Kensei Nagata,Akihiko Yoshimura +14 more
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TLDR
It is shown that the mRNA for the endogenous cytokine signaling repressor CIS3/SOCS3 is abundantly expressed in RA patients, and induction of CIS3 could represent a new approach for effective treatment of RA.Abstract:
Immune and inflammatory systems are controlled by multiple cytokines, including ILs and INFs. These cytokines exert their biological functions through Janus tyrosine kinases and STAT transcription factors. One such cytokine, IL-6, has been proposed to contribute to the development of rheumatoid arthritis (RA). We found that STAT3 was strongly tyrosine phosphorylated in synovial tissue of RA patients, but not those with osteoarthritis. Blockade of the IL-6-gp130-JAK-STAT3-signaling pathway might therefore be beneficial in the treatment of RA. We show here that the mRNA for the endogenous cytokine signaling repressor CIS3/SOCS3 is abundantly expressed in RA patients. To determine whether CIS3 is effective in treating experimental arthritis, a recombinant adenovirus carrying the CIS3 cDNA was injected periarticularly into the ankle joints of mice with antigen-induced arthritis or collagen-induced arthritis (CIA). Periarticular injection of CIS3 adenovirus drastically reduced the severity of arthritis and joint swelling compared with control groups. CIS3 was more effective than a dominant-negative form of STAT3 in the CIA model. Thus, induction of CIS3 could represent a new approach for effective treatment of RA.read more
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Evolving concepts of rheumatoid arthritis
TL;DR: Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis.
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Cytokines in atherosclerosis: pathogenic and regulatory pathways.
Alain Tedgui,Ziad Mallat +1 more
TL;DR: Based on the current knowledge of the role of cytokines in atherosclerosis, some novel therapeutic strategies to combat this disease are proposed and the potential of circulating cytokine levels as biomarkers of coronary artery disease is discussed.
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SOCS proteins, cytokine signalling and immune regulation.
TL;DR: This review brings together data from recent studies on SOCS proteins and their role in immunity, and proposes a cohesive model of how cytokine signalling regulates immune-cell function.
Journal ArticleDOI
Interleukin-6 and chronic inflammation.
TL;DR: Strategies targeting IL-6 andIL-6 signaling led to effective prevention and treatment of models of rheumatoid arthritis and other chronic inflammatory diseases.
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IL-6 in autoimmune disease and chronic inflammatory proliferative disease.
Katsuhiko Ishihara,Toshio Hirano +1 more
TL;DR: Evidence for the involvement of IL-6 in the pathophysiology of autoimmune diseases and chronic inflammatory proliferative diseases (CIPD) is reviewed and the possible molecular mechanisms of its involvement are discussed.
References
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