Mechanisms for HIV Tat upregulation of IL-10 and other cytokine expression: kinase signaling and PKR-mediated immune response.
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.
Li
James C B
JC
Immunology Research Laboratory, Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Lee
Davy C W
DC
Cheung
Benny K W
BK
Lau
Allan S Y
AS
D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D016207:Cytokines; D015696:Gene Products, tat; D016328:NF-kappa B; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; D051743:CCAAT-Enhancer-Binding Protein-delta; D019892:eIF-2 Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases