Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro
Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro
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DOI：
10.1073/pnas.95.13.7422
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发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Dinarello, CA
中科院分区：
文献类型：
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作者：
Shapiro, L;Heidenreich, KA;Dinarello, CA
促炎细胞因子白细胞介素（LL）-1和肿瘤坏死因子（TNF）在体外促进HIV 1型病毒复制。在目前的研究中，HIV的生产增加后，暴露于IL-1 β，渗透压，或表面粘附的巨噬细胞U1细胞系表达的HIV基因组，这表明促炎细胞因子和细胞应激的信号通路的汇合。p38丝裂原活化蛋白激酶（MAPK）介导细胞因子和应激反应，因此研究了这种激酶在HIV产生中的作用。通过p24抗原测量的HIV产生与p38 MAPK的特异性（非α）亚型表达的变化相关。在特异性p38 MAPK抑制剂（p38 inh）存在下，IL-1 β诱导的HIV产生被抑制超过90%，IL-1 β诱导的IL-8产生被完全抑制，两者的IC 50均为0.01 μ M。p38抑制以相似的程度阻断细胞相关的p24抗原和分泌的病毒。p38 inh还使新鲜感染的外周血单核细胞中的组成型HIV产生降低高达50%（P < 0.05：p38 MAPK活性的中断代表了抑制HIV的可行靶标。
The proinflammatory cytokines interleukin (LL)-1 and tumor necrosis factor (TNF) promote HIV type 1 viral replication in vitro. In the present studies, HIV production was increased in the macrophagic U1 cell line expressing the HIV genome after exposure to IL-1 beta, osmotic stress, or surface adhesion, suggesting a confluence of signaling pathways for proinflammatory cytokines and cell stressors. The p38 mitogen-activated protein kinase (MAPK) mediates both cytokine and stress responses; thus the role of this kinase in HIV production was investigated. HIV production as measured by p24 antigen correlated with changes in the expression of a specific (non-alpha) isoform of p38 MAPK. In the presence of a specific p38 MAPK inhibitor (p38 inh), IL-1 beta-induced HIV production was suppressed by more than 90% and IL-1 beta-induced IL-8 production was suppressed completely, both with IC50 of 0.01 mu M. p38 inhibition blocked cell-associated p24 antigen and secreted virus to a similar extent. The p38 inh also decreased constitutive HIV production in freshly infected peripheral blood mononuclear cells by up to 50% (P < 0.05:. Interruption of p38 MAPK activity represents a viable target for inhibition of HIV.