Proinflammatory cytokines regulate cyclooxygenase-2 mRNA expression in human macrophages

Biochem Biophys Res Commun. 1995 Mar 17;208(2):582-9. doi: 10.1006/bbrc.1995.1378.


Prostaglandins play a major role in the inflammatory and immune response. Macrophages constitutively produce prostaglandins by the enzyme cyclooxygenase-1 (cox) whereas inflammatory mediators and cytokines stimulate the inducible enzyme cox-2 for high output prostaglandin production. In this study, we investigated the effect of LPS, IFN-gamma and TNF-alpha in the regulation of cox-1 and cox-2 mRNA expression in PMA-differentiated U937 human macrophages. LPS, but not IFN-gamma or TNF-alpha, caused the induction of cox-2 mRNA in a dose- and time-dependent fashion. In IFN-gamma-primed macrophages, LPS stimulated a marked increase in the accumulation of cox-2 mRNA, whereas TNF-alpha and IFN-gamma induced a moderate level. However, IFN-gamma in combination with either LPS or TNF-alpha induced a synergistic increase in the accumulation of cox-2 mRNA after 24 hours. Regardless of the conditions, cox-1 mRNA remained unchanged. These results indicate that IFN-gamma priming is required for full expression of cox-2 mRNA in response to LPS or TNF-alpha stimulation and suggest that cox-2 mRNA is highly regulated by cytokines during macrophage activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Enzyme Induction
  • Gene Expression / drug effects
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / pharmacology*
  • Isoenzymes / genetics
  • Lipopolysaccharides / pharmacology
  • Macrophages / enzymology*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / genetics
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Isoenzymes
  • Lipopolysaccharides
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Prostaglandin-Endoperoxide Synthases