Regulation of activin-A production by human amnion, decidua and placenta in vitro by pro-inflammatory cytokines

Activin-beta A 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-1 beta (IL-I beta) 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/mu g protein/16 h, respectively (mean +/- SEM; n = 5-7 experiments). Both IL-1 beta and TNF-alpha stimulated activin-il production in a concentration-dependent fashion in all cultures; maximal stimulation was achieved at 0.25-1.0 ng/ml IL-1 beta and 25-50 ng/ml TNF-alpha, respectively;. In amnion, decidual and placental cultures IL-1 beta 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 actin-A measured in the sera of some n omen in preterm labour. (C) 1998 W. B. Saunders Company Ltd.