The effects of a cytokine suppressive anti-inflammatory drug on the output of prostaglandin E(2) and interleukin-1 beta from human fetal membranes

Mol Hum Reprod. 2002 Mar;8(3):281-5. doi: 10.1093/molehr/8.3.281.

Abstract

Fetal membranes are a primary source of prostaglandins and pro-inflammatory cytokines implicated in human parturition, so the inhibition of inflammatory pathways may be of benefit in pregnancies complicated by premature labour. We have therefore investigated the effects of a cytokine-suppressant anti-inflammatory drug (CSAID) on the output of prostaglandin E(2) (PGE(2)) and interleukin (IL)-1 beta from human fetal membranes in vitro. Bacterial endotoxin increased the expression of mRNA for IL-1 beta and type-2 cyclo-oxygenase (COX-2), and there were corresponding increases in the output of IL-1 beta protein and PGE(2). The CSAID decreased IL-1 beta protein, COX-2 expression and PGE(2) output, but not mRNA for IL-1 beta, indicating a post-translational effect on the production of IL-1 beta and a transcriptional affect on COX-2, with an overall reduction in PGE(2). These findings are consistent with the effects of CSAIDs in other systems, and indicate that they are of possible use in premature labour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Culture Techniques
  • Cyclooxygenase 2
  • Dinoprostone / genetics*
  • Extraembryonic Membranes / drug effects*
  • Extraembryonic Membranes / metabolism
  • Female
  • Gene Expression / drug effects*
  • Humans
  • Imidazoles / pharmacology*
  • Interleukin-1 / genetics*
  • Isoenzymes / genetics
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins
  • Pregnancy
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Thiazoles / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Imidazoles
  • Interleukin-1
  • Isoenzymes
  • Lipopolysaccharides
  • Membrane Proteins
  • Thiazoles
  • 6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone