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

Objective. To examine the effect of interleukin 17 (IL-17) on the 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-1 beta, tumor necrosis factor-alpha (TNF-alpha), 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, 41 9, IL-1 beta, TNF-alpha, and IL-6 was determined by real-time 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-1 beta, TNF-alpha and IL-6 were higher in the IL-17 and PBS groups than in normal DBA I 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-1 beta, and IL-6. Conclusion. TL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1 beta and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1 beta and IL-6 production are involved in the IL-17-induced aggravation of arthritis. (First Release Feb 15 2009; J Rheumatol 2009;36:684-92; doi: 10.3899/jrheum.080169)