title: The CCL2/CCR2 axis enhances vascular cell adhesion molecule-1 expression in human synovial fibroblasts.
abstract: 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).
  
  
  RESULTS
  Stimulation of OASFs with CCL2 induced VCAM-1 expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor (RS102895), PKCδ inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 increased PKCδ 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, PKCδ, p38MAPK, and AP-1 pathway promoted the adhesion of monocytes to the OASFs monolayer.
  
  
  CONCLUSIONS
  Our results suggest that CCL2 increases VCAM-1 expression in human OASFs via the CCR2, PKCδ, p38MAPK, c-Jun, and AP-1 signaling pathway. The CCL2-induced VCAM-1 expression promoted monocytes adhesion to human OASFs.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Chin-Jung
authors.initials: CJ
authors.lastname: Hsu
authors.forename: Yuan-Ya
authors.initials: YY
authors.lastname: Liao
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D007093:Imidazoles; D011725:Pyridines; D054390:Receptors, CCR2; D018808:Transcription Factor AP-1; D019010:Vascular Cell Adhesion Molecule-1; C085746:rottlerin; D048031:JNK Mitogen-Activated Protein Kinases; D048308:Mitogen-Activated Protein Kinase 14; C093642:SB 203580