The regulation of prostaglandin output from term intact fetal membranes by anti-inflammatory cytokines.
Prostaglandins are some of the main mediators which control parturition, and their production by intrauterine tissues can be up-regulated by pro-inflammatory cytokines. Anti-inflammatory cytokines may oppose these effects, and in this study we have investigated how two such cytokines affected fetal membrane function. Interleukin-10 (IL-10) inhibited the output of prostaglandin E2 (PGE2) from intact fetal membranes under basal and lipopolysaccharide (LPS)-stimulated conditions, and there was a parallel decrease in the expression of mRNA for COX-2. IL-10 also inhibited the production of interleukin-1beta (IL-1beta) and the expression of mRNA for IL-1beta, indicating that this cytokine has a broad anti-inflammatory effect. Transforming growth factor-beta1 (TGF-beta1), which is generally considered to be anti-inflammatory had opposite effects on PGE2 production, in that it increased the output of PGE2 for up to 8 hr. TGF-beta1 increased levels of type-2 cyclo-oxygenase (COX-2) and cytosolic phospholipase A2 (cPLA2) protein, and also activated the cPLA2 enzyme present; the profile of effects is similar to that of the pro-inflammatory cytokine IL-1beta, and was not expected. Combinations of TGF-beta1 with IL-1beta also increased PGE2 output and caused appropriate changes in prostaglandin pathway enzymes, whereas TGF-beta1 and IL-1alpha had more limited effects. Further studies are needed to establish the physiological significance of these findings, but TGF-beta1 does not seem to act as an inhibitory cytokine in intact fetal membranes at term.
Brown
N L
NL
Department of Maternal and Fetal Medicine, Institute of Obstetrics and Gynaecology, Division of Paediatrics, Obstetrics and Gynaecology, Imperial College School of Medicine, Queen Charlotte's and Chelsea Hospital, London, UK.
Alvi
S A
SA
Elder
M G
MG
Bennett
P R
PR
Sullivan
M H
MH
D002462:Cell Membrane / Q000201:enzymology; D046508:Culture Techniques; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D007743:Labor, Obstetric / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone