The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Salicylate Regulates Cyclooxygenase-2 Expression through ERK and Subsequent $NF-_kB$ Activation in Osteoblasts

  • Chae, Han-Jung (Department of Pharmacology and institute of Cardiovascular Research, School of Medicine, Chonbuk National, University) ;
  • Lee, Jun-Ki (Department of Dental Pharmacology and Wonkwng Biomaterial implant Research Institute, School of Dentistry, Wonkwang University) ;
  • Byun, Joung-Ouk (Department of Dental Pharmacology and Wonkwng Biomaterial implant Research Institute, School of Dentistry, Wonkwang University) ;
  • Chae, Soo-Wan (Department of Pharmacology and institute of Cardiovascular Research, School of Medicine, Chonbuk National, University) ;
  • Kim, Hyung-Ryong (Department of Dental Pharmacology and Wonkwng Biomaterial implant Research Institute, School of Dentistry, Wonkwang University)
  • Published : 2003.08.21
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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, $I{\kappa}B$ degradation and NF-${\kappa}B$ activation. The inhibition of the ERK pathway with selective inhibitor, PD098059, blocked cytokine-induced COX-2 expression and $PGE_2$ release. Salicylate treatment inhibited COX-2 expression induced by $TNF-{\alpha}$/$IFN-{\gamma}$ and regulated the activation of ERK, IKK and $I{\kappa}B$ degradation and subsequent NF-${\kappa}B$ 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-${\kappa}B$ 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, $I{\kappa}B$ degradation and NF-${\kappa}B$ activation independent of ROS release and suggested that salicylate exerts its anti-inflammatory action in part through inhibition of ERK, IKK, $I{\kappa}B$, $NF-{\kappa}B$ and resultant COX-2 expression pathway.

Keywords

References

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