|Title:||15-Deoxy- 12,14-Prostaglandin-J2 and Ciglitazone Inhibit Tnf- -Induced Matrix Metalloproteinase 13 Production Via the Antagonism of Nf- B Activation in Human Synovial Fibroblasts||Authors:||LIN, TZU-HUNG
|Issue Date:||2011||Journal Volume:||v.226||Journal Issue:||n.12||Start page/Pages:||3242-3250||Source:||JOURNAL OF CELLULAR PHYSIOLOGY||Abstract:||
Collagenase-3 (matrix metalloproteinase, MMP-13) plays an important role in the degradation of cartilage in pathologic conditions. MMP-13 is elevated in joint tissues in both rheumatoid arthritis (RA) and osteoarthritis (OA). In addition, inflammation-stimulated synovial fibroblasts are able to release MMP-13 and other cytokines in these diseases . The peroxisome proliferator-activated receptor- (PPAR ) ligands are recently considered as new anti-inflammatory compounds and these ligands were reported to ameliorate inflammatory arthritis. The aim of this study is to evaluate the mechanisms how PPAR ligands inhibit the inflammatory response in synovial fibroblasts. Two PPAR ligands, cyclopentenone prostaglandin 15-deoxy- 12,14-Prostaglandin J2 (15d-PGJ2) and synthetic thiazolidinedione compound ciglitazone were examined in this study. Here we found that 15d-PGJ2 and ciglitazone markedly inhibited TNF - -induced MMP-13 production in human synovial fibroblasts. In addition , activation of nuclear factor B (NF- B) is strongly associated with MMP -13 induction by TNF- and the activation of NF- B was determined by Western blot, reporter assay and immunofluorescence. It was found that 15d -PGJ2 markedly attenuated the translocation of NF- B by direct inhibition of the activation of IKK via a PPAR - independent manner. Ciglitazone also inhibits TNF- -induced MMP-13 expression by suppressing NF- B activation mainly via the modulation of p38-MAPK. Collectively, our data demonstrate that 15d-PGJ2 and ciglitazone attenuated TNF- - induced MMP-13 expression in synovial fibroblasts primarily through the modulation of NF- B signaling pathways. These compounds may have therapeutic application in inflammatory arthritis.
|Appears in Collections:||醫學系|
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