HO-1 induction by CO-RM2 attenuates TNF- α -induced cytosolic phospholipase A2 expression via inhibition of PKC α -dependent NADPH oxidase/ROS and NF- B

Pei Ling Chi, Chun Ju Liu, I-Ta Lee, Yu Wen Chen, Li Der Hsiao, Chuen Mao Yang

研究成果: 雜誌貢獻文章

23 引文 斯高帕斯(Scopus)

摘要

Rheumatoid arthritis (RA) is characterized by chronic inflammatory infiltration of the synovium and elevation of proinflammatory cytokines. Cytosolic phospholipase A2 (cPLA2) is involved in the development of inflammatory diseases. Heme oxygenase-1 (HO-1) has been shown to possess anti-inflammatory properties. The objective of the study was to investigate the detailed mechanisms of TNF-α-induced cPLA2 expression and to determine whether carbon monoxide releasing molecule-2 (CO-RM2) suppresses TNF-α-induced expression of NF-B-related proinflammatory genes, including cPLA2, via HO-1 induction in RA synovial fibroblasts (RASFs). Here, we reported that TNF-α-induced cPLA2 expression was mediated through TNFR1/PKCα-dependent signaling pathways, including NADPH oxidase (NOX) activation/ROS production and NF-B activation. CO-RM2 significantly suppressed TNF-α-induced cPLA 2 expression by inhibiting the ROS generation and the phosphorylation of NF-B p65 and IKKα/β, but not the phosphorylation of p38 MAPK and JNK1/2. These results were further confirmed by a ChIP assay to detect the NF-B DNA-binding activity. Our results demonstrated that induction of HO-1 by CO-RM2 exerted anti-inflammatory and antioxidant effects which were required in concert to prevent the activation of NF-B leading to induction of various inflammatory genes implicated in the pathogenesis of RA.
原文英語
文章編號279171
期刊Mediators of Inflammation
2014
DOIs
出版狀態已發佈 - 三月 5 2014
對外發佈Yes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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