PT - JOURNAL ARTICLE AU - Jun-Hee Lee AU - Mi-La Cho AU - Ju-In Kim AU - Young-Mee Moon AU - Hye-Jwa Oh AU - Geun-Tae Kim AU - Sun Ryu AU - Seung-Hoon Baek AU - Sun-Hee Lee AU - Ho-Youn Kim AU - Sung-Il Kim TI - Interleukin 17 (IL-17) Increases the Expression of Toll-like Receptor-2, 4, and 9 by Increasing IL-1β and IL-6 Production in Autoimmune Arthritis AID - 10.3899/jrheum.080169 DP - 2009 Feb 15 TA - The Journal of Rheumatology PG - jrheum.080169 4099 - http://www.jrheum.org/content/early/2009/02/12/jrheum.080169.short 4100 - http://www.jrheum.org/content/early/2009/02/12/jrheum.080169.full AB - Objective To examine the effect of interleukin 17 (IL-17) onthe expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice. Methods On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß,TNF-α, and IL-6 was determined by realtime RT-PCR. Results In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß,TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6. Conclusion IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17- induced aggravation of arthritis.