IL-10 production induced by HIV-1 Tat stimulation of human monocytes is dependent on the activation of PKC beta(II) and delta isozymes.
The effect of HIV-1 Tat protein on the production of IL-10, an immunosuppressive cytokine, was examined in human primary monocytes obtained from healthy HIV-1-negative blood donors. As expected and in agreement with our previous data, a dose-dependent induction of IL-10 was observed. In addition, we showed that this induction is mediated by the PKC pathway: in the presence of Ro 31-8220, an inhibitor of all PKC isozymes, or after 48 h of PMA treatment, Tat protein becomes unable to stimulate IL-10 production. Among the 11 PKC isozymes, eight (PKC alpha, beta(I), beta(II), delta, epsilon, eta, zeta, mu) are expressed in monocytes. In this study, by analyzing the translocation to the membrane after Tat stimulation, we showed that PKC alpha, beta(I), beta(II), delta and epsilon isozymes are activated by Tat. Moreover, by combining different approaches including selective PKC inhibitors (Gö6983, Gö6976, hispidin and rottlerin), we showed that PKC beta(II) and delta isozymes are essential for the activation of IL-10 production in human monocytes following stimulation by HIV-1 Tat protein.
Laboratoire d'immuno-virologie des lentivirus des primates, EA3038, Université Paul Sabatier, 118, route de Narbonne, 31062 Toulouse, France.
Xavier
X
Contreras
Yamina
Y
Bennasser
Elmostafa
E
Bahraoui
D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis*; D008301:Maleimides; D009000:Monocytes / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D011753:Pyrones / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; D000098:Acetophenones; D001578:Benzopyrans; D002227:Carbazoles; D004791:Enzyme Inhibitors; D015696:Gene Products, tat; D007211:Indoles; D008301:Maleimides; D011753:Pyrones; D054322:tat Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; C081021:Go 6976; C085746:rottlerin; C497258:PRKCD protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; C007946:hispidin; C064758:Ro 31-8220