The effects of a cytokine suppressive anti-inflammatory drug on the output of prostaglandin E(2) and interleukin-1 beta from human fetal membranes.
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.
Sullivan
M H F
MH
Institute of Reproductive and Developmental Biology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. mark.sullivan@ic.ac.uk
Alvi
S A
SA
Brown
N L
NL
Elder
M G
MG
Bennett
P R
PR
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D046508:Culture Techniques; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000235:genetics*; D005321:Extraembryonic Membranes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D013844:Thiazoles; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone