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FEBS Lett. 2005 Jun 6;579(14):3055-62.

Mechanisms for HIV Tat upregulation of IL-10 and other cytokine expression: kinase signaling and PKR-mediated immune response.

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Immunology Research Laboratory, Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.


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.

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