HIV-1 Tat protein induces TNF-alpha and IL-10 production by human macrophages: differential implication of PKC-betaII and -delta isozymes and MAP kinases ERK1/2 and p38
- PMID: 18692180
- DOI: 10.1016/j.cellimm.2008.06.011
HIV-1 Tat protein induces TNF-alpha and IL-10 production by human macrophages: differential implication of PKC-betaII and -delta isozymes and MAP kinases ERK1/2 and p38
Abstract
In this study, we demonstrate that HIV-1 Tat protein is able to induce IL-10 and TNF-alpha in human macrophages. We show that N-terminal Tat 1-45 fragment initiates the PKC pathway by acting at the membrane. Inhibition of PKC pathway, by chemical inhibitors or after PMA treatment, abolishes both IL-10 and TNF-alpha production. Among the eight PKC isoforms present in macrophages, we show that only PKC-betaIotaIota and -delta are activated by Tat or Tat 1-45 in human macrophages. However, their selective inhibition affects only IL-10 production. Downstream of PKC, Tat activates the MAP kinases p38 and ERK1/2 and the transcription factor NF-kappaB. Using chemical inhibitors we show that (i) both ERK1/2 MAP kinase and NF-kappaB transcription factor play an important role in IL-10 and TNF-alpha production, in macrophages stimulated by Tat. However, p38 MAP kinase seems to be involved only in IL-10 and not TNF-alpha production.
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