IL-4 regulates COX-2 and PGE2 production in human non-small cell lung cancer

Biochem Biophys Res Commun. 2006 May 19;343(4):995-1001. doi: 10.1016/j.bbrc.2006.03.073. Epub 2006 Mar 23.

Abstract

IL-4 is a type 2 cytokine that may mediate pleiotropic effects in the NSCLC microenvironment. Here, we investigated whether IL-4 regulates PGE(2) production in NSCLC cells. We found that IL-4 inhibited constitutive COX-2 expression and PGE(2) production in A427 and H2122 NSCLC cell lines, and also suppressed IL-1beta-induced COX-2 expression in A549 and RH2 NSCLC cell lines. COX-2 mRNA was decreased in response to IL-4, and promoter analysis indicated that IL-4 inhibited both constitutive and IL-1beta-induced COX-2 transcription. IL-4 inhibited IL-1beta-stimulated ERK phosphorylation, which may mediate the inhibition of IL-1beta-induced COX-2 by IL-4. IL-4 did not modulate additional arachidonic acid pathway enzymes mPGES-1 and 15-PGDH, which could potentially be responsible for regulating PGE(2) production. Overall, our studies demonstrate that IL-4 has the capacity to inhibit COX-2 mRNA transcription in NSCLC cells and the inhibition of PGE(2) appears to be predominately COX-2 dependent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Cyclooxygenase 2 / biosynthesis*
  • Dinoprostone / biosynthesis*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-4 / physiology*
  • Intramolecular Oxidoreductases / metabolism
  • Lung Neoplasms / metabolism*
  • Membrane Proteins / biosynthesis*
  • Phosphorylation
  • Prostaglandin-E Synthases
  • RNA, Messenger / metabolism
  • Signal Transduction

Substances

  • IL4 protein, human
  • Interleukin-1
  • Membrane Proteins
  • RNA, Messenger
  • Interleukin-4
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Extracellular Signal-Regulated MAP Kinases
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • Dinoprostone