Exogenous nef induces proinflammatory signaling events in murine macrophages
| Autor: | Zulema A. Percario, Paola Borghi, Giorgio Mangino, Florian A. Horenkamp, Elisabetta Affabris, Matthias Geyer, Valeria Serra |
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| Přispěvatelé: | Mangino, Giorgio, Serra, Valeria, Paola, Borghi, Percario, ZULEMA ANTONIA, Florian A., Horenkamp, Matthias, Geyer, Affabris, Elisabetta |
| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Chemokine Virulence Factors viruses Transgene media_common.quotation_subject Immunology Mice Transgenic Proinflammatory cytokine Mice Molecular Virology Virology Animals Humans Viral Immunology Secretion nef Gene Products Human Immunodeficiency Virus Internalization Cells Cultured media_common Mice Inbred BALB C virus-host interaction biology Macrophages virus diseases Macrophage Activation Phenotype Cell biology biology.protein HIV-1 Molecular Medicine Cytokines IRF3 Signal Transduction |
| Zdroj: | Viral immunology. 25(2) |
| ISSN: | 1557-8976 |
| Popis: | Despite the fact that murine cells are not permissive for human immunodeficiency virus type 1 (HIV-1) infection, several investigators have constructed transgenic (Tg) mice to model HIV-1-induced diseases to overcome this restriction. The generation of Tg mice expressing selected HIV-1 genes revealed that Nef harbors a major disease determinant. HIV-1 Nef protein is a molecular adapter able to interact with several cellular partners, interfering with cellular functions. The phenotype of Nef Tg mice was extensively characterized regarding in vivo development of AIDS-like disease and the effects of Nef expression in T lymphocytes, but the functions eventually corrupted by Nef in monocytes and macrophages was less studied. Nef treatment of human monocyte-derived macrophages induces the internalization of the protein and modulates the production and secretion of different chemokines and cytokines by activating specific intracellular signaling pathways (i.e., NF-jB, MAPK, and IRF3). Therefore we set up an in vitro murine macrophage-based model using stabilized cell lines and primary peritoneal macrophages, and treated them with recombinant myristoylated NefSF2 (recNef). Like human cells, murine macrophages responded to Nef treatment, activating IKK-a and IKK-b, JNK, and p38 MAP kinases. Activation of the NF-jB pathway is mandatory for the synthesis and release of a pool of cytokines and chemokines, including IFN-beta, that induce tyrosine phosphorylation of the signal transducer and activator of transcription (STAT)-1, STAT-2, and STAT-3, in an autocrine and paracrine manner, confirming that murine macrophages respond to Nef similarly to human ones. These data extend the results previously obtained in human primary macrophages, allowing the use of murine cells in culture to study signaling events modulated by Nef in myeloid-derived cells. In particular, it may be feasible to use macrophages derived from mice knocked out in specific signaling intermediates to obtain greater insight into the mechanism of Nef-induced effects. |
| Databáze: | OpenAIRE |
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