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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Leghmari K,Contreras X,Moureau C,Bahraoui E

doi

10.1016/j.cellimm.2008.06.011

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

46-55

issue

1

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(08)00117-2

journal_volume

254

pub_type

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