趨化素-2與人類滑液纖維母細胞血管上皮細胞表面黏著分子-1之關係

Chemokine ligand 2 (CCL2), also referred to monocyte chemoattractant protein-1 (MCP-1) or small inducible cytokine A2, belongs to the CC chemokine family that is associated with the disease status and outcomes of osteoarthritis (OA). Therefore, we investigated the intracellular signaling pathways involved in CCL2-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human OA synovial fibroblasts (OASFs). Human synovial fibroblasts, harvested from patients with osteoarthritis and with normal synovial tissues, and THP-1 cell line were cultured as specimens. Signal pathways were investigated with quantitative real-time PCR, western blot analysis, flow cytometry analysis, transfection of siRNAs, cell adhesion assay, and chromatin immnoprecipitation assay. Stimulation of OASFs with CCL2 induced VCAM-1 expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor (RS102895), PKC inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 increased PKC and p38MAPK activation. Treatment of OASFs with CCL2 increased the c-Jun phosphorylation and c-Jun binding to the AP-1 element on the VCAM-1 promoter as well. Furthermore, the CCL2-mediated CCR2, PKC, p38MAPK, and AP-1 pathway promoted the adhesion of monocytes to the OASF monolayer. Our results suggest that CCL2 increases VCAM-1 expression in human OASFs via the CCR2, PKC, p38MAPK, c-Jun, and AP-1 signaling pathway. The CCL2-induced VCAM-1 expression promoted monocyte adhesion to human OASFs.