Cyclic mechanical stretching and interleukin-1α synergistically up-regulate prostacyclin secretion in cultured human uterine myometrial cells

Prostacyclin (PGI₂), a potent uterine smooth muscle relaxant, is postulated to be a major prostaglandin (PG) secreted from the human myometrium. PGI₂ metabolite concentrations in the maternal plasma were reported to be elevated during pregnancy, especially during labor. Recently, we developed cultured human myometrial cells from pregnant women and reported that cyclic mechanical stretching mimicking labor increased PGI ₂ secretion from these cells by up-regulating PGI₂ synthase promoter activities. Since elevation of cervical/vaginal interleukin-1α (IL-1α) concentrations is also a characteristic feature of delivery, and IL-1α is a known stimulator of PG synthesis, we investigated a possible synergistic effect of cyclic mechanical stretching and IL-1α on PGI₂ production in cultured human myometrial cells. Treatment with IL-1α (10 ng/ml) significantly augmented (4- to 60-fold) the secretion of PGI₂, prostaglandin E₂ (PGE₂), prostaglandin F_2α (PGF_2α) and thromboxane A₂ (TXA₂) from cultured human myometrial cells obtained from non-pregnant and pregnant women as well as in cultured human umbilical artery and cultured human coronary artery smooth muscle cells (p < 0.05 for all comparisons). However, labor-like cyclic mechanical stretching up-regulated IL-1α-augmented PGI₂ secretion from myometrial cells obtained from non-pregnant and pregnant women 2.1- to 2.8-fold (p < 0.05 for all comparisons), but not PGE₂, PGF_2α nor TXA ₂. Moreover, such an augumentation of PGI₂ secretion by cyclic mechanical stretching was not observed in cultured human umbilical artery nor in cultured human coronary artery smooth muscle cells. These results suggest that cyclic mechanical stretching by labor, in concert with IL-1α stimulation, contributes to the increase in myometrial PGI₂ secretion during delivery.