Prostaglandin E2 suppresses bacterial killing in alveolar macrophages by inhibiting NADPH oxidase
Prostaglandin E2 suppresses bacterial killing in alveolar macrophages by inhibiting NADPH oxidase
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DOI：
10.1165/rcmb.2007-0153oc
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发表时间：
2007-11-01
影响因子：
6.4
通讯作者：
Peters-Golden, Marc
中科院分区：
文献类型：
--
作者：
Serezani, Carlos H.;Chung, Jooho;Peters-Golden, Marc
前列腺素E-2（PGE（2））是一种有效的脂质介质，通过连接四种不同的G蛋白偶联的E前列腺素（EP）受体（EP 1-EP 4）来影响细胞功能的变化。前列腺素E2抑制肺泡巨噬细胞（AM）的细菌杀伤和活性氧中间体（ROI）的产生，但其分子机制知之甚少。本研究的目的是评估PGE 2抑制AM杀伤肺炎克雷伯菌的分子机制和特异性EP受体。用PGE_2处理AM可抑制K.这种作用被腺苷酸环化酶抑制剂阻断，并被刺激性G蛋白（G（s））偶联的EP 2和EP 4受体的激动剂模拟。相反，通过用环氧合酶抑制剂、吲哚美辛和EP 2和EP 4的拮抗剂预处理来增强杀微生物活性。在检查1101生产时发现了类似的结果。PGE 2抑制杀伤和ROI生成与其激活cAMP效应子、蛋白激酶A和cAMP-1直接激活的交换蛋白以及减弱还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶组分p47 phox磷酸化和易位至吞噬体膜相关。我们的结论是，前列腺素E2通过G1-偶联的EP 2/EP 4受体抑制AM的杀微生物活性，增加cAMP抑制p47 phox的组装和激活。
Prostaglandin E-2 (PGE(2)) is a potent lipid mediator that effects changes in cell functions through ligation of four distinct G protein-coupled E prostanoid (EP) receptors (EP1-EP4). PGE2 inhibits bacterial killing and reactive oxygen intermediate (ROI) production by alveolar macrophages (AMs), although little is known about the operative molecular mechanisms. The aims of this study were to evaluate the molecular mechanisms and the specific EP receptors through which PGE2 inhibits killing of Klebsiella pneumoniae by AMs. The treatment of AMs with PGE2 suppressed the killing of K. pneumoniae, and this effect was blocked by an adenylyl cyclase inhibitor and mimicked by agonists for the stimulatory G protein (G(s))-coupled EP2 and EP4 receptors. Conversely, microbicidal activity was augmented by pretreatment with the cyclooxygenase inhibitor, indomethacin, and antagonists of EP2 and EP4. Similar results were found when 1101 production was examined. PGE2 inhibition of killing and ROI generation was associated with its activation of the CAMP effectors, protein kinase A and exchange protein directly activated by cAMP-1, as well as attenuation of the phosphorylation and translocation of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component, p47phox, to the phagosomal membrane. We conclude that PGE2 suppresses the microbicidal activity of AMs through the G,-coupled EP2/EP4 receptors, with increased CAMP inhibiting the assembly and activation of p47phox.