Li James C B, Lee Davy C W, Cheung Benny K W, Lau Allan S Y
Immunology Research Laboratory, Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
FEBS Lett. 2005 Jun 6;579(14):3055-62. doi: 10.1016/j.febslet.2005.04.060.
HIV Tat has been known to have multiple regulatory roles including replication of HIV and modulation of cellular kinases. We investigated whether signaling kinase PKR plays a critical role in mediating Tat-induced cytokine dysregulation. We showed Tat induction of IL-10 dysregulation is associated with PKR activation. To examine the mechanism involved, inhibition of PKR activity abrogated the Tat-induced cytokine induction. We next identified that the MAP kinases including ERK-1/2 and p38 are downstream of PKR in these Tat-induced pathways. Thus, PKR may play a critical role in mediating the subversive effects of HIV Tat resulting in IL-10 induction.
已知HIV反式激活因子（Tat）具有多种调节作用，包括HIV复制及细胞激酶调节。我们研究了信号激酶PKR在介导Tat诱导的细胞因子失调中是否起关键作用。我们发现Tat诱导的白细胞介素-10（IL-10）失调与PKR激活有关。为研究其中涉及的机制，抑制PKR活性可消除Tat诱导的细胞因子诱导作用。接下来我们确定，在这些Tat诱导的信号通路中，包括细胞外信号调节激酶1/2（ERK-1/2）和p38在内的丝裂原活化蛋白激酶（MAP激酶）是PKR的下游分子。因此，PKR可能在介导HIV Tat导致IL-10诱导的破坏作用中起关键作用。
