Salicylate regulates COX-2 expression through ERK and subsequent NF-kappaB activation in osteoblasts.

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Chae HJ, Chae SW, Reed JC, Kim HR

Salicylate regulates COX-2 expression through ERK and subsequent NF-kappaB activation in osteoblasts.

Immunopharmacol Immunotoxicol. 2004 Feb;26(1):75-91.

PubMed ID

15106733 [ View in PubMed

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Abstract

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 IkappaB degradation and subsequent NF-kappaB 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-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 the ERK, IKK, IkappaB, NF-kappaB and resultant COX-2 expression pathway.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Magnesium salicylate	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Inhibitor	Details
Salicylic acid	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Inhibitor	Details