Pregnancy

Tumor Necrosis Factor Alpha Stimulates Adenylyl Cyclase Activity in Human Myometrial Cells

Abstract

Cytokines such as tumor necrosis factor (TNF) have been implicated in amniotic fluid infections and preterm and term labor. The underlying mechanisms are incompletely understood. In some smooth muscle cells, TNF affects function of the ß-adrenergic/adenylyl cyclase pathway. The present study was performed to examine the effects of chronic TNF exposure on adenylyl cyclase activity in cell cultures of human myometrium. Chronic TNF exposure led to a dose- and time-dependent increase in basal-, GTP-, NaF-, and forskolin-stimulated adenylyl cyclase activity. The increase in adenylyl cyclase activity was not mediated by changes in the expression of the heterotrimeric G proteins G_s or G_i as determined by immunoblotting. In addition, increases in adenylyl cyclase activity occurred in the presence of indomethacin, indicating that these changes were not provoked by TNF-induced changes in prostaglandin production. The present results suggest that TNF-induced increases in adenylyl cyclase activity, in human myometrial cells obtained from the lower uterine segment, occur at the level of G-protein/adenylyl cyclase interaction or at the level of the adenylyl cyclase enzyme itself.