期刊
CELLULAR IMMUNOLOGY
卷 253, 期 1-2, 页码 45-53出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2008.04.015
关键词
HIV-1; Tat; human monocytes; TNF-alpha; IL-10; PKC-delta; p38MAP kinase
资金
- Agence Nationale de Recherche sur le SIDA
- Conseil Regional Midi-Pyrenees
- SIDACTION
- Universite Paul Sabatier
- Toulouse
HIV-1 Tat protein stimulates the production of both TNF-alpha and IL-10 in human monocytes. Taking into account the ability of TNF-alpha to induce IL-10 production, we evaluated the link between Tat, TNF-alpha and IL-10 and the implication of PKC and p38 MAP kinase pathways. Our data showed that (i) in the presence of neutralizing anti-TNF-alpha antibodies, IL-10 production is only partially inhibited; (ii) in a calcium-free medium, while TNF-alpha production is totally inhibited, Tat continues to induce IL-10: (iii) under these conditions, Tat-mediated IL-10 production is associated with PKC-delta activation; and (iv) downstream of PKC, p38 MAP kinase is crucial for TNF-a independent IL10 production. Overall, our data suggest a new mechanism, implicating Tat protein, by which HIV-1 may maintain a constant production of the immunosuppressive IL-10 cytokine, even in the absence of TNF-alpha. production. In consequence, HIV-1 may escape immune surveillance and thus promote the establishment of an immunosuppressive state. (C) 2008 Elsevier Inc. All rights reserved.
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