Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis

被引:178
作者
Shouda, T
Yoshida, T
Hanada, T
Wakioka, T
Oishi, M
Miyoshi, K
Komiya, S
Kosai, K
Hanakawa, Y
Hashimoto, K
Nagata, K
Yoshimura, A [1 ]
机构
[1] Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Higashi Ku, Fukuoka 8128582, Japan
[2] Kurume Univ, Fac Med, Dept Orthoped Surg, Kurume, Fukuoka 830, Japan
[3] Kurume Univ, Fac Med, Dept Internal Med 2, Kurume, Fukuoka 830, Japan
[4] Kagoshima Univ, Fac Med, Dept Orthoped Surg, Kagoshima, Japan
[5] Gifu Univ, Sch Med, Dept Regenerat Cardiovasc Syst, Gifu 500, Japan
[6] Ehime Univ, Sch Med, Dept Dermatol, Shitukawa, Japan
关键词
D O I
10.1172/JCI13568
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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-gp 130-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.
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收藏
页码:1781 / 1788
页数:8
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