Tat protein of human immunodeficiency virus type 1 induces interleukin-10 in human peripheral blood monocytes: Implication of protein kinase C-dependent pathway
Tat protein of human immunodeficiency virus type 1 induces interleukin-10 in human peripheral blood monocytes: Implication of protein kinase C-dependent pathway
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DOI：
10.1128/jvi.74.22.10551-10562.2000
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发表时间：
2000-11-01
影响因子：
5.4
通讯作者：
Bahraoui, E
中科院分区：
文献类型：
--
作者：
Badou, A;Bennasser, Y;Bahraoui, E
在人类免疫缺陷病毒1型（HIV-1）感染患者中观察到的临床表现主要是由于病毒及其组分破坏免疫系统的能力。HIV-1达特蛋白可能参与了这种免疫系统紊乱。这种蛋白质由HIV感染患者的感染细胞分泌，并在血浆中游离，在血浆中它可以相互作用并被感染和未感染的细胞吸收。在HIV-1感染的无症状患者中，白细胞介素-10（IL-10）（一种高度免疫抑制的细胞因子）的产生与疾病进展为AIDS相关。在本工作中，我们测试了达特诱导健康供体外周血单核细胞产生IL-10的能力。结果表明，达特以剂量和刺激时间依赖性方式引起IL-10的产生。对信号转导机制的研究表明，（i）钙通道不参与或仅轻微参与Tat诱导的IL-10产生，（ii）蛋白激酶C通道起重要作用，和（iii）达特刺激单核细胞导致转录因子NF-κ B核内易位和诱导促分裂原活化蛋白激酶ERK 1和ERK 2磷酸化;蛋白激酶C的这两种潜在底物的活化是产生IL-10所必需的。最后，我们的研究结果表明，达特的效果是在膜水平上发挥作用，活性结构域位于N-末端残基1至45。这种由达特诱导的IL-10的产生可能参与了HIV感染向AIDS的进展。
The clinical manifestations observed in human immunodeficiency virus type 1 (HIV-l)-infected patients are primarily due to the capacity of the virus and its components to inactivate the immune system. HIV-1 Tat protein could participate in this immune system disorder. This protein is secreted by infected cells of HIV-infected patients and is free in the plasma, where it can interact and be taken up by both infected and noninfected cells. In asymptomatic patients infected by HIV-1, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with disease progression to AIDS. In the present work, we tested the capacity of Tat to induce IL-10 production by peripheral blood monocytes of healthy donors. The results show that Tat causes the production of IL-10 in a dose- and stimulation time-dependent manner. Investigations of the mechanisms involved in signal transduction show that (i) the calcium pathway is not or only slightly involved in Tat-induced IL-10 production, (ii) the protein kinase C pathway plays an essential role, and (iii) monocyte stimulation by Tat results in the intranuclear translocation of transcription factor NF-KappaB and in the induction of phosphorylation of the mitogen-activated protein kinases ERK1 and ERK2; activation of these two potential substrates of protein kinase C is required for the production of IL-10. Finally, our results suggest that the effect of Tat is exerted at the membrane level and that the active domain is located within N-terminal residues 1 to 45. This production of IL-10 induced by Tat could participate in the progression of HIV infection to AIDS.