title: CTGF increases IL-6 expression in human synovial fibroblasts through integrin-dependent signaling pathway.
abstract: BACKGROUND
  Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. CTGF is abundantly expressed in osteoarthritis (OA). However, the relationship between CTGF and IL-6 in OA synovial fibroblasts (OASFs) is mostly unknown.
  
  
  RESULTS
  OASFs showed significant expression of CTGF, and expression was higher than in normal SFs. OASFs stimulation with CTGF induced concentration-dependent increases in IL-6 expression. CTGF mediated IL-6 production was attenuated by αvβ5 integrin neutralized antibody and apoptosis signal-regulating kinase 1 (ASK1) shRNA. Pretreatment with p38 inhibitor (SB203580), JNK inhibitor (SP600125), AP-1 inhibitors (Curcumin and Tanshinone IIA), and NF-κB inhibitors (PDTC and TPCK) also inhibited the potentiating action of CTGF. CTGF-mediated increase of NF-κB and AP-1 luciferase activity was inhibited by SB203580 and SP600125 or ASK1 shRNA or p38 and JNK mutant.
  
  
  CONCLUSIONS
  Our results suggest that CTGF increased IL-6 production in OASFs via the αvβ5 integrin, ASK1, p38/JNK, and AP-1/NF-κB signaling pathways.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shan-Chi
authors.initials: SC
authors.lastname: Liu
authors.forename: Chin-Jung
authors.initials: CJ
authors.lastname: Hsu
authors.forename: Hsien-Te
authors.initials: HT
authors.lastname: Chen
authors.forename: Hsi-Kai
authors.initials: HK
authors.lastname: Tsou
authors.forename: Show-Mei
authors.initials: SM
authors.lastname: Chuang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D055513:Connective Tissue Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013583:Synovial Membrane / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D019030:Receptors, Vitronectin; D018808:Transcription Factor AP-1; C064660:integrin alphaVbeta5; D055513:Connective Tissue Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human