Prostaglandin E2 inhibits replication of HIV-1 in macrophages through activation of protein kinase A
Prostaglandin E2 inhibits replication of HIV-1 in macrophages through activation of protein kinase A
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DOI：
10.1016/s0008-8749(02)00017-5
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发表时间：
2002-01-01
影响因子：
4.3
通讯作者：
Coffey, MJ
中科院分区：
文献类型：
--
作者：
Hayes, MM;Lane, BR;Coffey, MJ
由于巨噬细胞是艾滋病患者PGE(2)增加的来源，我们研究了PGE(2)在这些细胞中复制HIV-1中的作用。通过逆转录酶检测，PGE2抑制人单核细胞源性巨噬细胞（MDM）中HIV-1复制。用PGE(1)类似物米索前列醇、腺苷酸环化酶激活剂福斯克林和环AMP类似物二丁基环AMP （db-cAMP）治疗MDM可抑制HIV复制。蛋白激酶A （PKA）激活剂8-溴环AMP也能抑制HIV-1的复制。在不依赖于进入的潜伏hiv感染的U1细胞中观察到类似的结果。在PGE(2)治疗后，HIV-1 mRNA水平也有相应的下降。用载体CMV共转染HIV-1启动子LTR荧光素酶。表达PKA催化单元的Calpha增加了PKA活性，降低了HIV-1启动子活性。pMT对PKA活性的抑制。RAB载体，PKA的突变调控单元，增强HIV-1启动子活性。综上所述，PGE(2)通过pka依赖性机制抑制MDM中HIV-1基因的表达。(C) 2002 Elsevier Science （USA）。版权所有。
Since macrophages are a source of increased PGE(2) in AIDS, we investigated the role of PGE(2) in the replication of HIV-1 in these cells. PGE2 inhibited HIV-1 replication measured by reverse transcriptase in human monocyte-derived macrophage (MDM). Treatment of MDM with the PGE(1) analog misoprostol, the adenylate cyclase activator forskolin, and the cyclic AMP analog dibutyryl-cyclic AMP (db-cAMP) suppressed HIV replication. The protein kinase A (PKA) activator 8-bromo-cyclic AMP also inhibited HIV-1 replication. Similar results were observed with the entry-independent, latently HIV-infected U1 cells. There was a parallel decrease in HIV-1 mRNA levels following PGE(2) treatment. Co-transfection of the HIV-1 promoter LTR luciferase, with the vector CMV.Calpha, which expresses the PKA catalytic unit increasing PKA activity, reduced HIV-1 promoter activity. Inhibition of PKA activity with the pMT.RAB vector, a mutant regulatory unit of PKA, augmented HIV-1 promoter activity. In summary, PGE(2) inhibits HIV-1 gene expression in MDM through a PKA-dependent mechanism. (C) 2002 Elsevier Science (USA). All rights reserved.