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 extrap lacental membranes at term and preterm. The regulation of activin-A pr oduction 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 enzym e dispersion and treated in primary culture with interleukin-1 beta (I L-I beta) and tumour necrosis factor-alpha (TNF-alpha). Activin-A prod uction (determined by ELISA) by amnion, decidual and placental culture s 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 a nd TNF-alpha stimulated activin-il production in a concentration-depen dent 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 amni on, decidual and placental cultures IL-1 beta stimulated activin-A pro duction to 747 +/- 274, 190 +/- 11 and 254 +/- 60.2 per cent of contro ls, 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-inflamma tory cytokines are potent stimulators of activin-A production by intra uterine tissues. This may provide an explanation for the elevated conc entrations of actin-A measured in the sera of some n omen in preterm l abour. (C) 1998 W. B. Saunders Company Ltd.