Sodium salicylate inhibits expression of COX-2 through suppression of ERK and subsequent NF-kappaB activation in rat ventricular cardiomyocytes.
The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation, which can be inhibited with sodium salicylate. IL-1beta and TNF-alpha can induce extracellular signal-regulated kinase (ERK), IKK, IkappaB degradation and NF-kappaB activation. Salicylate inhibited the IL-1beta and TNF-alpha-induced COX-2 expressions, regulated the activation of ERK, IKK and IkappaB degradation, and the subsequent activation of NF-kappaB, in neonatal rat ventricular cardiomyocytes. The inhibition of the ERK pathway, with a selective inhibitor, PD098059, blocked the expressions of IL-1beta and TNF-alpha-induced COX-2 and PGE2 release. The antioxidant, N-acetyl-cysteine, also reduced the glutathione or catalase- attenuated COX-2 expressions in IL-1beta and TNF-alpha-treated cells. This antioxidant also inhibited the activation of ERK and NF-kappaB in neonatal rat cardiomyocytes. In addition, IL-1beta and TNF-alpha stimulated the release of reactive oxygen species (ROS) in the cardiomyocytes. However, salicylate had no inhibitory effect on the release of ROS in the DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, IkappaB degradation and NF-kappaB activation, independently of the release of ROS, which suggested that salicylate exerts its anti-inflammatory action through the inhibition of ERK, IKK, IkappaB and NF-kappaB, and the resultant COX-2 expression pathway in neonatal rat ventricular cardiomyocytes.
Kwon
Keun-Sang
KS
Department of Preventive Medicine, Chonbuk National University, Medical School, Chonju 560-180, Korea.
Chae
Han-Jung
HJ
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016328:NF-kappa B; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D012980:Sodium Salicylate