HIV‐1 Tat protein induces interleukin‐10 in human peripheral blood monocytes: involvement of protein kinase C‐βII and ‐δ

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Abstract
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-α, PKC-βΙΙ, PKC-δ, and PKC-ε, 2) of these four potential candidates, only PKC-βΙΙ, PKC-δ, and PKC-ε 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-α and PKC-ε by specific antisense oligonucleotides has no effect on Tat-mediated IL-10 induction, inhibition of either PKC-βΙΙ or PKC-δ partially inhibits IL-10 production; and 4) the simultaneous inhibition of PKC-βΙΙ and PKC-δ totally inhibits Tat-mediated IL-10. Altogether, these results suggest that the induction of IL-10 by Tat is strictly dependent on the PKC-δ and -βII isoforms.—Bennasser, Y., Bahraoui, E. HIV-1 Tat protein induces interleukin 10 in human peripheral blood monocytes: involvement of protein kinase C-βII and -δ.
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  • Styrelsen för Internationellt Utvecklingssamarbete
  • Sidaction