Activin A exerts both pro- and anti-inflammatory effects on human term gestational tissues.
There is a growing appreciation of the importance of activin as a modulator of immune function. The aim of the present study was to determine whether activin A exerts any effects on cytokine and prostaglandin (PG) production by the tissues of pregnancy. Explant cultures were established for amnion, choriodecidual and placental tissues derived from pregnancies delivered at term by Caesarean section (n=5 placentae). Explants were treated with activin A (0.5, 5 and 50 ng/ml) in serum-free Ham's F12/DME media for 24 h (n=3-4 replicates). Production rates of interleukin (IL)-1beta, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and PGE(2)were determined using immunoassay. Differences between treatment groups were analysed by ANOVA followed by Dunnett's test;P< 0.05 was considered to be significant. Amnion IL-6 production exhibited biphasic responses to activin A: at 5 ng/ml activin A, IL-6 production was significantly stimulated (to 246+/-74.6 per cent of control (mean+/-sem), while at 50 ng/ml it was significantly inhibited (to 46+/-7.4 per cent of control). IL-8 and PGE(2)production by amnion showed significant responses to activin A that were similar to those of IL-6. No significant effects of activin A were observed on choriodecidual and placental IL-6, IL-8 and PGE(2)production. However, TNF-alpha production was significantly inhibited by 50 ng/ml activin A in both choriodecidual and placental explants (to 43+/-9.7 per cent and 51+/-6.7 per cent of control, respectively). Placental IL-1beta production was not altered by treatment with activin A at any concentration. These findings support the concept of activin as an immune modulator in tissues of pregnancy.
Keelan
J A
JA
Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Auckland, New Zealand.
Zhou
R L
RL
Mitchell
M D
MD
D028341:Activins; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000650:Amnion / Q000187:drug effects / Q000276:immunology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002823:Chorion / Q000187:drug effects / Q000276:immunology; D046508:Culture Techniques; D003656:Decidua / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D005321:Extraembryonic Membranes / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007265:Inhibins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D010920:Placenta / Q000187:drug effects* / Q000276:immunology*; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D028341:Activins; D007265:Inhibins; D015232:Dinoprostone