CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling PathwayReport as inadecuate




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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.

Methodology-Principal Findings

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-Significance

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.



Author: Shan-Chi Liu, Chin-Jung Hsu, Hsien-Te Chen, Hsi-Kai Tsou, Show-Mei Chuang , Chih-Hsin Tang

Source: http://plos.srce.hr/



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