Regulation of activin-A production by human amnion, decidua and placenta in vitro by pro-inflammatory cytokines.
Activin-betaA subunits are expressed by the human placenta and extraplacental membranes at term and preterm. The regulation of activin-A production by these tissues has not been characterized to date, however. To determine the effects on activin-A production of pro-inflammatory cytokines, amnion, decidual and placental cells were isolated by enzyme dispersion and treated in primary culture with interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). Activin-A production (determined by ELISA) by amnion, decidual and placental cultures was 1.2 +/-0.27, 31.1+/-9.9, and 50.7+/-28.5 pg/microg protein/16 h, respectively (mean+/-SEM; n=5-7 experiments). Both IL-1beta and TNF-alpha stimulated activin-A production in a concentration-dependent fashion in all cultures; maximal stimulation was achieved at 0.25-1.0 ng/ml IL-1beta and 25-50 ng/ml TNF-alpha, respectively. In amnion, decidual and placental cultures IL-1beta stimulated activin-A production to 747+/-274, 190+/-11, and 254+/-60.2 per cent of controls, while TNF-alpha stimulated production to 312+/-81.5, 194+/-22.5, and 193+/-12.5 per cent, respectively (mean+/-SEM; n=5; P<0.05 by ANOVA). These studies show for the first time that pro-inflammatory cytokines are potent stimulators of activin-A production by intrauterine tissues. This may provide an explanation for the elevated concentrations of activin-A measured in the sera of some women in preterm labour.
Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, New Zealand. j.keelan@auckland.ac.nz
J A
JA
Keelan
N P
NP
Groome
M D
MD
Mitchell
D028341:Activins; D000328:Adult; D000650:Amnion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003656:Decidua / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006133:Growth Substances; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D028341:Activins; D005576:Colforsin; D007265:Inhibins; D013755:Tetradecanoylphorbol Acetate