Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc

Toxicol Appl Pharmacol. 2008 Sep 1;231(2):260-6. doi: 10.1016/j.taap.2008.04.012. Epub 2008 Apr 29.


Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. Cyclooxygenase 2-derived eicosanoids are important modulators of airway inflammation. In this study, we characterized the transcriptional and posttranscriptional events that regulate COX-2 expression in a human bronchial epithelial cell line BEAS-2B exposed to Zn2+. Zn2+ exposure resulted in pronounced increases in COX-2 mRNA and protein expression, which were prevented by pretreatment with the transcription inhibitor actinomycin D, implying the involvement of transcriptional regulation. This was supported by the observation of increased COX-2 promoter activity in Zn2+-treated BEAS-2B cells. Mutation of the cAMP response element (CRE), but not the kappaB-binding sites in the COX-2 promoter markedly reduced COX-2 promoter activity induced by Zn2+. Inhibition of NFkappaB activation did not block Zn2+-induced COX-2 expression. Measurement of mRNA stability demonstrated that Zn2+ exposure impaired the degradation of COX-2 mRNA in BEAS-2B cells. This message stabilization effect of Zn2+ exposure was shown to be dependent on the integrity of the 3'-untranslated region found in the COX-2 transcript. Taken together, these data demonstrate that the CRE and mRNA stability regulates COX-2 expression induced in BEAS-2B cells exposed to extracellular Zn2+.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Bronchi / cytology
  • Bronchi / drug effects
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclooxygenase 2 / drug effects*
  • Cyclooxygenase 2 / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Mutation
  • NF-kappa B / metabolism
  • RNA Stability / drug effects*
  • RNA, Messenger / drug effects*
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects
  • Zinc / toxicity*


  • Cyclic AMP Response Element-Binding Protein
  • NF-kappa B
  • RNA, Messenger
  • Cyclooxygenase 2
  • Zinc