%0 Journal Article
%T The CCL2/CCR2 Axis Enhances Vascular Cell Adhesion Molecule-1 Expression in Human Synovial Fibroblasts
%A Yu-Min Lin
%A Chin-Jung Hsu
%A Yuan-Ya Liao
%A Ming-Chih Chou
%A Chih-Hsin Tang
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0049999
%X Background Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of osteoarthritis (OA). Here, we investigated the intracellular signaling pathways involved in CCL2-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human OA synovial fibroblasts (OASFs). Methodology/Principal Findings Stimulation of OASFs with CCL2 induced VCAM-1 expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor (RS102895), PKC¦Ä inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 increased PKC¦Ä and p38MAPK activation. Treatment of OASFs with CCL2 also increased the c-Jun phosphorylation and c-Jun binding to the AP-1 element on the VCAM-1 promoter. Moreover, CCL2-mediated CCR2, PKC¦Ä, p38MAPK, and AP-1 pathway promoted the adhesion of monocytes to the OASFs monolayer. Conclusions/Significance Our results suggest that CCL2 increases VCAM-1 expression in human OASFs via the CCR2, PKC¦Ä, p38MAPK, c-Jun, and AP-1 signaling pathway. The CCL2-induced VCAM-1 expression promoted monocytes adhesion to human OASFs.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0049999