Production of prostaglandin F2α by cultured bovine endometrial cells in response to tumor necrosis factor α:: Cell type specificity and intracellular mechanisms
Production of prostaglandin F2α by cultured bovine endometrial cells in response to tumor necrosis factor α:: Cell type specificity and intracellular mechanisms
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DOI：
10.1095/biolreprod62.5.1116
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发表时间：
2000-05-01
影响因子：
3.6
通讯作者：
Okuda, K
中科院分区：
文献类型：
--
作者：
Skarzynski, DJ;Miyamoto, Y;Okuda, K
肿瘤坏死因子α(TNFα)是牛子宫内膜分泌前列腺素(PG)F-2α的有效刺激因子。本研究的目的是确定子宫内膜(上皮或间质细胞)中负责分泌PGF(2α)的细胞类型，以及TNFa作用的细胞内机制。培养的牛上皮和间质细胞暴露于肿瘤坏死因子α(0.006-6 nM)或催产素(100 NM)4h后，间质细胞(P<；0.001)中前列腺素F(2α)的产生呈剂量依赖性增加，但对上皮细胞无明显影响。另一方面，催产素可刺激上皮细胞产生PGF(2α)，但对间质细胞则无刺激作用。当基质细胞与肿瘤坏死因子α和磷脂酶C或磷脂酶(2)抑制剂共同孵育24 h时，只有磷脂酶(2)抑制剂能完全阻断肿瘤坏死因子α的作用(P<；0.001)。当基质细胞暴露于肿瘤坏死因子α和花生四烯酸时，肿瘤坏死因子α的作用增强(P<；0.001)。当基质细胞与一氧化氮供体(S-NAP)孵育24 h时，S-NAP以剂量依赖的方式刺激PGF(2α)的产生。尽管一氧化氮合酶抑制剂L抑制了肿瘤坏死因子α刺激的前列腺素F(2α)的产生，但磷酸二酯酶抑制剂却增强了肿瘤坏死因子α和S-NAP的作用(P<；0.05)。结果表明，肿瘤坏死因子α刺激牛子宫内膜间质细胞产生前列腺素F(2α)的靶点是子宫内膜间质细胞，其作用是通过激活聚乳酸和花生四烯酸转化来实现的。此外，肿瘤坏死因子α可能通过诱导一氧化氮合酶和随后的NO-cGMP的形成而对前列腺素F(2α)的产生产生刺激作用。
Tumor necrosis factor alpha (TNF alpha) has been shown to be a potent stimulator of prostaglandin (PG) F-2 alpha secretion in the bovine endometrium. The aims of the present study were to determine the cell types in the endometrium (epithelial or stromal cells) responsible for the secretion of PGF(2 alpha) in response to TNF alpha, and the intracellular mechanisms of TNFa action. Cultured bovine epithelial and stromal cells were exposed to TNF alpha (0.006-6 nM) or oxytocin (100 nM) for 4 h. TNF alpha resulted in a dose-dependent increase of PGF(2 alpha) production in the stromal cells (P < 0.001) but not in the epithelial cells. On the other hand, oxytocin stimulated PGF(2 alpha) output in the epithelial cells but not in the stromal cells. When the stromal cells were incubated for 24 h with TNF alpha and inhibitors of phospholipase (PL) C or PLA(2) only PLA(2) inhibitor completely stopped the actions of TNF alpha (P < 0.001). When the stromal cells were exposed to TNF alpha and arachidonic acid, the action of TNF alpha was augmented (P < 0.001). When the stromal cells were incubated for 24 h with a nitric oxide (NO) donor (S-NAP), S-NAP stimulated the PGF(2 alpha) production dose-dependently. Although an NO synthase (NOS) inhibitor (L-NAME) reduced TNF alpha-stimulated PGF(2 alpha) production, an inhibitor of phosphodiesterase augmented the actions of TNF alpha and S-NAP (P < 0.05). The overall results indicate that the target of TNF alpha for stimulation of PGF(2 alpha) production in cattle is the endometrial stromal cells, and that the actions of TNF alpha are mediated via the activation of PLA, and arachidonic acid conversion. Moreover, TNF alpha may exert a stimulatory effect on PGF(2 alpha) production via the induction of NOS and the subsequent NO-cGMP formation.