PT  - JOURNAL ARTICLE
AU  - A Yokota
AU  - M Narazaki
AU  - Y Shima
AU  - N Murata
AU  - T Tanaka
AU  - M Suemura
AU  - K Yoshizaki
AU  - H Fujiwara
AU  - I Tsuyuguchi
AU  - T Kishimoto
TI  - Preferential and persistent activation of the STAT1 pathway in rheumatoid synovial fluid cells.
DP  - 2001 Sep 01
TA  - The Journal of Rheumatology
PG  - 1952--1959
VI  - 28
IP  - 9
4099  - http://www.jrheum.org/content/28/9/1952.short
4100  - http://www.jrheum.org/content/28/9/1952.full
SO  - J Rheumatol2001 Sep 01; 28
AB  - OBJECTIVE: Inflammatory cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor-alpha are produced in great quantities in inflamed rheumatoid joints. However, little is known about the pathogenic significance of each cytokine in the proliferative synovitis and destruction of bone and joint. We investigated the role of cytokine receptor signals transduced into cells at the foci of rheumatoid inflammation. METHODS: Synovial fluid (SF) cells from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were examined for the activation of a group of cytokine receptor signaling molecules, signal transducers and activators of transcription (STAT). RESULTS: DNA binding of STAT1 in SF cells was observed in 8 out of 14 patients with RA, but in none of the 10 patients with OA studied, and this was prevented by preincubation of these cells with neutralizing anti-IL-6 antibody. IL-6 activated both STAT1 and STAT3 in normal peripheral blood (PB) leukocytes, and preferentially STAT1 in rheumatoid SF cells. Moreover, STAT1 activation in rheumatoid SF cells appeared to be continuous, in contrast to the transient activation in normal PB leukocytes. CONCLUSION: STAT1 and STAT3 are differentially regulated in response to IL-6 in different cell types. The continuous STAT1 activation may be of pathogenic significance in the progression and persistence of RA.