Title : Heme oxygenase 1 attenuates interleukin-1β-induced cytosolic phospholipase A2 expression via a decrease in NADPH oxidase/reactive oxygen species/activator protein 1 activation in rheumatoid arthritis synovial fibroblasts.

Pub. Date : 2012 Jul

PMID : 22231145






7 Functional Relationships(s)
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1 The aim of this study was to examine the mechanisms underlying interleukin-1beta (IL-1beta)-induced cytosolic phospholipase A2 (cPLA2) expression through ROS generation as modulated by HO-1 in RA synovial fibroblasts (RASFs). Reactive Oxygen Species interleukin 1 beta Mus musculus
2 The aim of this study was to examine the mechanisms underlying interleukin-1beta (IL-1beta)-induced cytosolic phospholipase A2 (cPLA2) expression through ROS generation as modulated by HO-1 in RA synovial fibroblasts (RASFs). Reactive Oxygen Species interleukin 1 beta Mus musculus
3 METHODS: IL-1beta-induced ROS generation was determined by flow cytometry. Reactive Oxygen Species interleukin 1 beta Mus musculus
4 The involvement of MAPKs and NADPH oxidase (NOX)/ROS in IL-1beta-induced cPLA2 expression was investigated using pharmacologic inhibitors and transfection with small interfering RNAs (siRNAs) and was analyzed by Western blotting and promoter assay. Reactive Oxygen Species interleukin 1 beta Mus musculus
5 RESULTS: IL-1beta-induced cPLA2 expression was mediated through NOX activation/ROS production, which was attenuated by N-acetylcysteine (NAC; a scavenger of ROS), the inhibitors of NOX (diphenyleneiodonium chloride and apocynin), MEK-1/2 (U0126), and JNK-1/2 (SP600125), transfection with the respective siRNAs, and the overexpression of HO-1 in RASFs. Reactive Oxygen Species interleukin 1 beta Mus musculus
6 RESULTS: IL-1beta-induced cPLA2 expression was mediated through NOX activation/ROS production, which was attenuated by N-acetylcysteine (NAC; a scavenger of ROS), the inhibitors of NOX (diphenyleneiodonium chloride and apocynin), MEK-1/2 (U0126), and JNK-1/2 (SP600125), transfection with the respective siRNAs, and the overexpression of HO-1 in RASFs. Reactive Oxygen Species interleukin 1 beta Mus musculus
7 CONCLUSION: In RASFs, IL-1beta induced cPLA2 expression via activation of p42/p44 MAPK and JNK-1/2, leading to p47phox phosphorylation, ROS production, and AP-1 activation. Reactive Oxygen Species interleukin 1 beta Mus musculus