Involvement of mitogen-activated protein kinases and peroxisome proliferator-activated receptor γ in monosodium urate crystal-induced vascular cell adhesion molecule 1 expression in human rheumatoid arthritis synovial fibroblasts

Abstract

To investigate whether monosodium urate (MSU) crystals could induce the production of VCAM-1 (vascular cell adhesion molecule1) in human synovial cells and its possible signaling pathways, human synovial cells isolated from synovial tissue explants were stimulated with various doses of MSU crystals for different time intervals. Expression of VCAM-1 was evaluated with Western blotting. To explore the underlying mechanisms, VCAM-1 protein expression was also evaluated after activation of several signaling molecules including mitogen-activated protein kinases (MAPKs) and peroxisome proliferator-activated receptorγ (PPARγ) were blocked. Exposure of synovial cells to MSU crystals induced VCAM-1 expression in culture medium in a dose- and time-dependent manner, reaching a plateau at 1000µM and 24h. Inhibition of the activation of MAPKs and PPARγ could block this increase. The present results demonstrated that MSU crystals could induce VCAM-1 expression. MAPKs and PPARγ signaling pathways regulated the induced VCAM-1 expression.