Leishmania donovani-induced macrophages cyclooxygenase-2 and prostaglandin E2 synthesis
Leishmania donovani-induced macrophages cyclooxygenase-2 and prostaglandin E2 synthesis
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DOI：
10.1046/j.1365-3024.2001.00372.x
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发表时间：
2001-04-01
影响因子：
2.2
通讯作者：
Olivier, M
中科院分区：
文献类型：
--
作者：
Matte, C;Maion, G;Olivier, M
前列腺素E-2（PGE（2））分泌在利什曼原虫感染的报告。然而，介导这种反应的信号传导机制还没有很好地理解。由于环氧合酶-2（考克斯-2）和胞质磷脂酶A（2）（cPLA（2））参与了对各种刺激的PGE（2）合成，因此在利什曼原虫感染的佛波醇肉豆蔻酸酯醋酸酯分化的U937人单核细胞系中评价了这些酶的意义。时程实验表明，PGE（2）的合成显着增加平行考克斯-2的表达，当细胞培养在杜氏利什曼原虫前鞭毛体或脂多糖（LPS）的存在。cPLA（2）mRNA的表达仅在LPS刺激时增加。考克斯-2、蛋白酪氨酸激酶（PTK）和蛋白激酶C（PKC）的拮抗剂吲哚美辛、金雀异黄素和H7可抑制L. donovani和LPS。但只有H7抑制考克斯-2 mRNA的合成，且PGE（2）抑制与考克斯-2表达减少之间存在显著相关性。总之，我们的结果表明，L. donovani导致PGE（2）的产生，部分是通过涉及考克斯-2表达的PKC依赖性信号通路。他们进一步揭示，PTK依赖性事件是利什曼原虫诱导的PGE 2产生所必需的，但不是考克斯-2表达所必需的。更好地了解利什曼原虫诱导PGE（2）产生的机制可以深入了解利什曼病的病理生理学，并有助于改善治疗方法。
Prostaglandin E-2 (PGE(2)) secretion during Leishmania infection has been reported. However the signalling mechanisms mediating this response are not well understood. Since cyclooxygenase-2 (COX-2) and cytosolic phospholipase A(2) (cPLA(2)) are involved in PGE(2) synthesis in response to various stimuli, the implication of these enzymes was evaluated in Leishmania-infected phorbol myristate acetate-differentiated U937 human monocytic cell line. Time-course experiments showed that PGE(2) synthesis increased significantly in parallel with COX-2 expression when cells were incubated in the presence of Leishmania donovani promastigotes or lipopolysaccharides (LPS). Increase in cPLA(2) mRNA expression was only detected when cells were stimulated with LPS. Indomethacin, genistein, and H7, which are antagonists of COX-2, protein tyrosine kinase (PTK) and protein kinase C (PKC), respectively, inhibited PGE(2) production induced by L. donovani and LPS. However only H7 inhibited COX-2 mRNA synthesis, and there was a significant correlation between PGE(2) inhibition and reduced COX-2 expression. Collectively, our results indicate that infection of U937 by L. donovani leads to the generation of PGE(2) in part through a PKC-dependent signalling pathway involving COX-2 expression. They further reveal that PTK-dependent events are necessary for Leishmania-induced PGE2 generation, but not for COX-2 expression. A better understanding of the mechanisms by which Leishmania can induce PGE(2) production could provide insight into the pathophysiology of leishmaniasis and may help to improve therapeutic approaches.