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The regulation of prostaglandin output from term intact fetal membranes byanti‐inflammatory cytokines
Author(s) -
Brown N. L.,
Alvi S. A.,
Elder M. G.,
Bennett P. R.,
Sullivan M. H. F.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00942.x
Subject(s) - cytokine , endocrinology , lipopolysaccharide , medicine , proinflammatory cytokine , prostaglandin , phospholipase a2 , prostaglandin e , prostaglandin e2 , interleukin , eicosanoid , transforming growth factor , fetal membrane , biology , inflammation , chemistry , fetus , enzyme , biochemistry , placenta , arachidonic acid , pregnancy , genetics
Summary 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 E 2 (PGE 2 ) 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‐1β (IL‐1β) and the expression of mRNA for IL‐1β, indicating that this cytokine has a broad anti‐inflammatory effect. Transforming growth factor‐β1 (TGF‐β1), which is generally considered to be anti‐inflammatory had opposite effects on PGE 2 production, in that it increased the output of PGE 2 for up to 8 hr. TGF‐β1 increased levels of type‐2 cyclo‐oxygenase (COX‐2) and cytosolic phospholipase A 2 (cPLA2) protein, and also activated the cPLA 2 enzyme present; the profile of effects is similar to that of the pro‐inflammatory cytokine IL‐1β, and was not expected. Combinations of TGF‐β1 with IL‐1β also increased PGE 2 output and caused appropriate changes in prostaglandin pathway enzymes, whereas TGF‐β1 and IL‐1α had more limited effects. Further studies are needed to establish the physiological significance of these findings, but TGF‐β1 does not seem to act as an inhibitory cytokine in intact fetal membranes at term.