Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CCAAT-Enhancer-Binding Protein-delta
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CCAAT-Enhancer-Binding Proteins / metabolism
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Cells, Cultured
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Cytokines / biosynthesis
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Cytokines / genetics*
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Cytokines / immunology
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Cytokines / metabolism*
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Dose-Response Relationship, Drug
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Gene Products, tat / metabolism*
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HIV-1
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Humans
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Interleukin-10 / biosynthesis
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Leukocytes / metabolism
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MAP Kinase Signaling System*
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NF-kappa B / metabolism
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Time Factors
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Transcription Factors / metabolism
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Up-Regulation
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eIF-2 Kinase / antagonists & inhibitors
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eIF-2 Kinase / immunology*
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eIF-2 Kinase / metabolism*
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p38 Mitogen-Activated Protein Kinases / metabolism
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tat Gene Products, Human Immunodeficiency Virus
Substances
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CCAAT-Enhancer-Binding Proteins
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CEBPD protein, human
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Cytokines
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Gene Products, tat
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NF-kappa B
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Transcription Factors
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tat Gene Products, Human Immunodeficiency Virus
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Interleukin-10
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CCAAT-Enhancer-Binding Protein-delta
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eIF-2 Kinase
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases