Hypertonic sodium chloride induction of cyclooxygenase-2 occurs independently of NF-κB and is inhibited by the glucocorticoid receptor in A549 cells

  • Won C
  • Park M
  • Bahn J
 et al. 
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Abstract

Cellular response to a hypertonic environment is important for fluid clearance in the lung. Hypertonicity modulates prostaglandin synthesis by influencing cyclooxygenase-2 (COX-2) expression in tissues such as liver and kidney via a mitogen-activated protein kinase (MAPK)-dependent pathway. However, little is known about COX-2 expression in response to hypertonicity in the lung. COX-2 mRNA accumulation induced by hypertonic NaCl was detected after 1 h of treatment, and COX-2 mRNA continued to accumulate until 18 h, the longest time point examined, in human alveolar epithelial A549 cells. This induction was a transcriptional event that occurred in the absence of the protein synthesis inhibitor cycloheximide and was the result of enhanced promoter activity, as examined with the use of full-length COX-2 promoter-driven reporter plasmids. The induction of COX-2 expression by hypertonic NaCl did not require the activation of NF-κB. The p38 MAPK inhibitor, SB203580, or MEK1/2 inhibitor, U0126, inhibited hypertonic induction of COX-2 expression. We examined whether the hypertonic induction of COX-2 was under the influence of glucocorticoid; we found that COX-2 promoter activity and mRNA and protein levels were depressed by dexamethasone and antagonized by the glucocorticoid receptor (GR) antagonist RU486. Our data demonstrate that the induction of COX-2 expression by hypertonic NaCl occurs independently of NF-κB and is inhibited by the GR in A549 cells. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Author-supplied keywords

  • Alveolar epithelial cells
  • COX-2
  • Glucocorticoid receptor
  • Hypertonic sodium chloride
  • NF-κB

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Authors

  • Chung Lim Won

  • Mikyung Park

  • Jae Jun Bahn

  • Hiroyasu Inoue

  • Young Joo Lee

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