Salicylate Regulates COX-2 Expression Through ERK and Subsequent NF-κB Activation in Osteoblasts

• Published in: Immunopharmacology and immunotoxicology 2004, Vol.26 (1), p.75-91
• Main Authors: Chae, Han-Jung, Chae, Soo-Wan, Reed, John C., Kim, Hyung-Ryong
• Format: Article
• Language: English
• Subjects: Cyclooxygenase-2 (COX-2); Nuclear factor-κB (NF-κB); Osteoblast; Salicylate
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1081/IPH-120029946

The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation and can be inhibited with sodium salicylate. TNF-α plus IFN-γ can induce extracellular signal-regulated kinase (ERK), IKK, IκB degradation and NF-κB 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-α IFN-γ and regulated the activation of ERK, IKK and IκB degradation and subsequent NF-κB activation in MC3T3E1 osteoblasts. As well, antioxidant-catalase, N-acetyl-cysteine or reduced glutathione-attenuated COX-2 expression in combined cytokines-treated cells. These antioxidants also inhibited the activation of ERK, IKK and NF-κB in MC3T3E1 osteoblasts. In addition, TNF-α IFN-γ 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, IκB degradation and NF-κB activation independent of ROS release and suggested that salicylate exerts its anti-inflammatory action in part through inhibition of the ERK, IKK, IκB, NF-κB and resultant COX-2 expression pathway.