In:
Mediators of Inflammation, Wiley, Vol. 2014 ( 2014), p. 1-18
Abstract:
Rheumatoid arthritis (RA) is characterized by chronic inflammatory infiltration of the synovium and elevation of proinflammatory cytokines. Cytosolic phospholipase A 2 (cPLA 2 ) 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 cPLA 2 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 cPLA 2 , via HO-1 induction in RA synovial fibroblasts (RASFs). Here, we reported that TNF- α -induced cPLA 2 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 cPLA 2 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.
Type of Medium:
Online Resource
ISSN:
0962-9351
,
1466-1861
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
1137605-3
detail.hit.zdb_id:
2008065-7
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