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Sodium salicylate inhibits expression of COX-2 through suppression of ERK and subsequent NF-κB activation in Rat ventricular cardiomyocytes

Abstract

The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation, which can be inhibited with sodium salicylate. IL-1β and TNF-α can induce extracellular signal-regulated kinase (ERK), IKK, IκB degradation and NF-κB activation. Salicylate inhibited the IL-1β and TNF-α-induced COX-2 expressions, regulated the activation of ERK, IKK and IκB degradation, and the subsequent activation of NF-κB, in neonatal rat ventricular cardiomyocytes. The inhibition of the ERK pathway, with a selective inhibitor, PD098059, blocked the expressions of IL-1β and TNF-α-induced COX-2 and PGE2 release. The antioxidant,N-acetyl-cys-teine, also reduced the glutathione or catalase- attenuated COX-2 expressions in IL-1β and TNF-α-treated cells. This antioxidant also inhibited the activation of ERK and NF-κB in neonatal rat cardiomyocytes. In addition, IL-1β and TNF-α 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, IκB degradation and NF-κB activation, independently of the release of ROS, which suggested that salicylate exerts its anti-inflammatory action through the inhibition of ERK, IKK, IκB and NF-κB, and the resultant COX-2 expression pathway in neonatal rat ventricular cardiomyocytes.

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Correspondence to Keun -Sang Kwon or Han -Jung Chae.

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Kwon, K.-., Chae, H.-. Sodium salicylate inhibits expression of COX-2 through suppression of ERK and subsequent NF-κB activation in Rat ventricular cardiomyocytes. Arch Pharm Res 26, 545–553 (2003). https://doi.org/10.1007/BF02976879

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Key words

  • Cyclooxygenase-2
  • Nuclear factor-kappaB
  • N-acetyl-L-cysteine
  • Reactive oxygen species
  • Interleukin-1
  • Tumor necrosis factor
  • Nas sodium salicylate