HO-1 Induction by CO-RM2 Attenuates TNF-α-Induced Cytosolic Phospholipase A2 Expression via Inhibition of PKCα-Dependent NADPH Oxidase/ROS and NF-κB. (29th January 2014)

• Record Type: Journal Article
• Authors: Chi, Pei-Ling; Liu, Chun-Ju; Lee, I-Ta; Chen, Yu-Wen; Hsiao, Li-Der; Yang, Chuen-Mao
• Other Names: Manna Sunil Kumar Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2014(2014)
• Publication Date: 2014-01-29
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2014/279171
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : 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- κ 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/PKC α -dependent signaling pathways, including NADPH oxidase (NOX) activation/ROS production and NF- κ B activation. CO-RM2 significantly suppressed TNF- α -induced cPLA2 expression by inhibiting the ROS generation and the phosphorylation of NF- κ B p65 and IKK α / β, but not the phosphorylation of p38 MAPK and JNK1/2. These results were further confirmed by a ChIP assay to detect the NF- κ 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- κ B leading to induction of various inflammatory genes implicated in the pathogenesis of RA.