HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes:: involvement of protein kinase C-βII and -δ
HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes:: involvement of protein kinase C-βII and -δ
复制标题
DOI：
10.1096/fj.01-0775com
复制
发表时间：
2002-04-01
期刊：
影响因子：
4.8
通讯作者：
Bahraoui, E
中科院分区：
文献类型：
--
作者：
Bennasser, Y;Bahraoui, E
在HIV感染患者中，白细胞介素-10（IL-10）（一种高度免疫抑制的细胞因子）的产生与疾病向AIDS的进展相关。我们先前已经证明HIV-1达特通过蛋白激酶C（PKC）依赖性途径诱导人单核细胞产生IL-10。在这里，我们表明，PKC激活达特是必不可少的IL-10的诱导。在存在于人单核细胞中的八种PKC亚型中，我们研究了哪种亚型在Tat介导的IL-10产生中起关键作用，并显示1）达特可激活PKC-α、PKC-β II、PKC-δ和PKC-β，2）在这四种潜在候选物中，只有PKC-β II、PKC-δ和PKC-β被活性结构域达特1-45激活，其负责IL-10的产生并通过长期暴露于PMA而被耗尽，PMA消除了Tat介导的IL-10的产生，3）尽管通过特异性反义寡核苷酸选择性抑制PKC-α和PKC-β II对Tat介导的IL-10诱导没有影响，但抑制PKC-β II或PKC-δ部分抑制IL-10的产生;和4）同时抑制PKC-β II和PKC-δ完全抑制Tat介导的IL-10。总之，这些结果表明，诱导IL-10的达特是严格依赖于PKC-δ和β II亚型。
In HIV-infected patients, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with the disease progression toward AIDS. We have previously shown that HIV-1 Tat induces IL-10 production by human monocytes via a protein kinase C (PKC)-dependent pathway. Here we show that PKC activation by Tat is essential for IL-10 induction. Among the eight PKC isoforms present in human monocytes, we investigated which isoform(s) plays this crucial role in Tat-mediated IL-10 production and show that 1) Tat can activate PKC-alpha, PKC-betaII, PKC-delta, and PKC-epsilon, 2) of these four potential candidates, only PKC-betaII, PKC-delta, and PKC-epsilon are activated by the active domain Tat 1-45, which is responsible for IL-10 production and depleted by long-term exposure to PMA, which abolishes Tat-mediated IL-10 production, 3) whereas selective inhibition of PKC-alpha and PKC-epsilon by specific antisense oligonucleotides has no effect on Tat-mediated IL-10 induction, inhibition of either PKC-betaII or PKC-delta partially inhibits IL-10 production; and 4) the simultaneous inhibition of PKC-betaII and PKC-delta totally inhibits Tat-mediated IL-10. Altogether, these results suggest that the induction of IL-10 by Tat is strictly dependent on the PKC-delta and -betaII isoforms.