HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes: involvement of protein kinase C-betaII and -delta.
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.
Bennasser
Yamina
Y
Laboratoire d'Immuno-Virologie, EA 3038, Université Paul Sabatier, 31062 Toulouse, France.
Bahraoui
Elmostafa
E
D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015696:Gene Products, tat / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D021381:Protein Transport; D054322:tat Gene Products, Human Immunodeficiency Virus
D004791:Enzyme Inhibitors; D015696:Gene Products, tat; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D054322:tat Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; C497258:PRKCD protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta