The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation and can be inhibited with sodium salicylate. TNF-alpha plus IFN-gamma can induce extracellular signal-regulated kinase (ERK), IKK, IkappaB degradation and NF-kappaB activation. The inhibition of the ERK pathway with selective inhibitor, PD098059, blocked cytokine-induced COX-2 expression and PGE2 release. Salicylate treatment inhibited COX-2 expression induced by TNF-alpha/IFN-gamma and regulated the activation of ERK, IKK and I kappaB degradation and subsequent NF-kappaB activation in MC3T3E1 osteoblasts. Furthermore, antioxidants such as catalase, N-acetyl-cysteine or reduced glutathione attenuated COX-2 expression in combined cytokines-treated cells, and also inhibited the activation of ERK, IKK and NF-kappaB in MC3T3E1 osteoblasts. In addition, TNF-alpha/IFN-gamma stimulated ROS release in the osteoblasts. However, salicylate had no obvious effect on ROS release in DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, IkappaB degradation and NF-kappaB activation independent of ROS release and suggested that salicylate exerts its anti-inflammatory action in part through inhibition of ERK, IKK, IkappaB, NF-kappaB and resultant COX-2 expression pathway.
Antioxidants ; Catalase ; Cyclooxygenase 2* ; Dinoprostone ; Glutathione ; Inflammation ; MAP Kinase Signaling System ; NF-kappa B* ; Osteoblasts* ; Phosphotransferases ; Sodium Salicylate ; Tumor Necrosis Factor-alpha