The production of interleukin-1beta from human fetal membranes is not obligatory for increased prostaglandin output.
Bacterial endotoxin increased the expression of mRNA (maximal after 4 hr) for interleukin-1beta (IL-1beta) and the release of mature protein from intact human fetal membranes. In contrast, the change in expression of mRNA for type 2 cyclo-oxygenase (COX-2) was biphasic, with peaks after 0.5-1 hr and after 8 hr of culture. An antibody to IL-1beta was without effect after 4 hr of culture, inhibited endotoxin-stimulated prostaglandin E2 (PGE2) production after 8 hr of culture, and caused a parallel decrease in the expression of mRNA for COX-2. We conclude that endotoxin induced the expression of COX-2 through IL-1beta-independent and IL-1beta-dependent mechanisms, and these differences are time dependent. Corticotrophin-releasing hormone (CRH) or platelet-activating factor (PAF) also increased the expression of mRNA for IL-1beta and the release of IL-1beta from some, but not all, fetal membranes. The antibody to IL-1beta did not affect CRH-stimulated or PAF-stimulated PGE2 production or COX-2 expression. We conclude that CRH and PAF can induce the expression of IL-1beta, but this is not obligatory for increased PGE2 release, and the effect of these stimuli on COX-2 expression is a direct, IL-1beta-independent effect.
Alvi
S A
SA
Department of Maternal and Fetal Medicine, Division of Paediatrics, Obstetrics & Gynaecology, Imperial College School of Medicine, Queen Charlotte's & Chelsea Hospital, London, UK.
Rajasingam
D
D
Brown
N L
NL
Elder
M G
MG
Bennett
P R
PR
Sullivan
M H
MH
D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D046508:Culture Techniques; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D010972:Platelet Activating Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone