Cole O F, Seki H, Elder M G, Sullivan M H
R.P.M.S. Institute of Obstetrics and Gynaecology, Hammersmith Hospital, London, UK.
Biochim Biophys Acta. 1995 Nov 9;1269(2):139-44. doi: 10.1016/0167-4889(95)00107-4.
Interleukin-1 beta (IL-1 beta) increased the production of cyclic AMP and prostaglandin E2 (PGE2) by cultured human decidual cells during 24 h of stimulation, but not over short incubation times (< 6 h). At concentrations of IL-1 beta ranging from 1 to 100 pg/ml, there were parallel changes in cyclic AMP and PGE2 levels, but 1000 pg of IL-1 beta/ml inhibited cyclic AMP production while still stimulating PGE2 synthesis. The possible link between cyclic AMP and PGE2 was therefore studied further. Inhibition of IL-1 beta-stimulated PGE2 synthesis by indomethacin and direct addition of PGE2 had no effect on cyclic AMP levels, indicating that PGE2 did not increase cyclic AMP production by human decidual cells and confirming the independent synthesis of cyclic AMP and PGE2. The increase in cyclic AMP production induced by IL-1 beta is dependent on protein synthesis, but it is not known which component of the adenylate cyclase is increased. A phosphodiesterase inhibitor potentiated the effects of IL-1 beta on cyclic AMP synthesis, indicating that the cytokine may increase cyclic AMP metabolism. We suggest that high concentrations of IL-1 beta activate phosphodiesterase activity more than adenylate cyclase, which gives rise to the low levels of cyclic AMP noted above. IL-1 beta also decreased forskolin-stimulated cyclic AMP production, which again indicates increased cyclic AMP metabolism. Since most concentrations of IL-1 beta alone increased cyclic AMP levels, this stimulation must out-weigh the increase in metabolism apparent in the presence of forskolin, phosphodiesterase inhibitor or high levels of interleukin. It is clear that IL-1 beta increased decidual PGE2 production independently of cyclic AMP, and that other second messenger must mediate the action of this cytokine.
在24小时的刺激过程中，白细胞介素-1β（IL-1β）可增加培养的人蜕膜细胞中环磷酸腺苷（cAMP）和前列腺素E2（PGE2）的生成，但在较短的孵育时间（<6小时）内则不会。在1至100 pg/ml的IL-1β浓度范围内，cAMP和PGE2水平呈平行变化，但1000 pg/ml的IL-1β会抑制cAMP生成，同时仍刺激PGE2合成。因此，对cAMP和PGE2之间的可能联系进行了进一步研究。吲哚美辛对IL-1β刺激的PGE2合成的抑制以及PGE2的直接添加对cAMP水平没有影响，这表明PGE2不会增加人蜕膜细胞中cAMP的生成，并证实了cAMP和PGE2的独立合成。IL-1β诱导的cAMP生成增加依赖于蛋白质合成，但尚不清楚腺苷酸环化酶的哪个成分增加。一种磷酸二酯酶抑制剂增强了IL-1β对cAMP合成的作用，这表明细胞因子可能增加cAMP代谢。我们认为，高浓度的IL-1β对磷酸二酯酶活性的激活作用大于对腺苷酸环化酶的激活作用，这导致了上述低水平的cAMP。IL-1β还降低了福斯高林刺激的cAMP生成，这再次表明cAMP代谢增加。由于大多数单独的IL-1β浓度会增加cAMP水平，这种刺激作用必定超过在存在福斯高林、磷酸二酯酶抑制剂或高水平白细胞介素时明显增加的代谢作用。很明显，IL-1β独立于cAMP增加蜕膜PGE2的生成，并且其他第二信使必定介导了这种细胞因子的作用。
