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

Takanori Shouda, Takafumi Yoshida, Toshikatsu Hanada, Toru Wakioka, Masanobu Oishi, Kanta Miyoshi, Setsuro Komiya, Ken Ichiro Kosai, Yasushi Hanakawa, Koji Hashimoto, Kensei Nagata, Akihiko Yoshimura

Research output: Contribution to journalArticlepeer-review

318 Citations (Scopus)

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 antigeninduced 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.

Original languageEnglish
Pages (from-to)1781-1788
Number of pages8
JournalJournal of Clinical Investigation
Volume108
Issue number12
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Medicine(all)

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