Abstract
Abstract IL-17 producing Th17 has a key role in the pathogenesis of autoimmune inflammation. Among various cytokines which are interwoven with the IL-17 pathway, members of IL-1beta family including IL-18 have recently gained significance. In the present study, we stimulated synovial fibroblasts with the combination of IL-17 and IL-18, and quantified the cellular production of stromal cell-derived factor-1 (SDF-1) with ELISA and its mRNA with RT-PCR. Both IL-17 and IL-18 significantly increased the level of SDF-1, not only individually but also synergistically (p<0.05). The synergism was effectively suppressed by anti-IL-17, anti-IL-18 antibodies and PI3K inhibitor. In conclusion, PI3K-dependent synergism between IL-18 and IL-17 is first observed in this study, and adds a novel perspective for the role of IL-18 in immune regulation. The two cytokines’ individual effects, mutual interaction and synergism draw a crisscrossing map between IL-1 family and IL-17.
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