Effect of IL-17 for Monocyte Chemotactic Protein Production by Human Temporomandibular Joint Synovial Fibroblasts

Abstract

IL-17, which is produced primarily by Th17 cells, has recently emerged as a key player in the pathogenesis of numerous autoimmune and inflammatory diseases. The effects of IL-17

in temporomandibular disorders(TMD)were investigated using gene expression profiling of synovial fibroblasts isolated from TMD patients. Microarray analysis indicated that CCL8(also called monocyte chemotactic protein 2; MCP-2)was found to be the most highly upregulated gene by IL-17 among the genes with known functions. The MCP chemokines,MCP-1, MCP-2, and MCP-3, have considerable structural homology and are members of the cysteine–cysteine(C-C)chemokine family that mainly modulates monocyte/macrophage recruitment in multiple inflammatory diseases. Real-time PCR analysis showed that the gene expressions of MCP-1, MCP-2, and MCP-3 were significantly higher in IL-17-treated synovial fibroblasts than in non-treated controls. MCP-1 protein production was increased by IL-17 in a time-dependent manner. Additionally, the protein production of MCP-1 was increased by IL-17 treatment in synovial fibroblast samples isolated from three TMD patients. Furthermore, IL-17 signaling was mainly through the NF􀎺B activation pathway for MCP-1 production in synovial fibroblasts. These results suggest that the MCP chemokine production by IL-17 is likely to contribute to promotion of the inflammatory condition in TMD.