CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells

MicroRNA-mediated regulation of gene expression appears to be involved in a variety of cellular processes, including development, differentiation, proliferation, and apoptosis. Mir-146a is thought to be involved in the regulation of the innate immune response, and its expression is increased in tiss...

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Published inThe FASEB journal Vol. 24; no. 7; pp. 2292 - 2300
Main Authors Rom, Slava, Rom, Inna, Passiatore, Giovanni, Pacifici, Marco, Radhakrishnan, Sujatha, Del Valle, Luis, Piña-Oviedo, Sergio, Khalili, Kamel, Eletto, Davide, Peruzzi, Francesca
Format Journal Article
LanguageEnglish
Published United States The Federation of American Societies for Experimental Biology 01.07.2010
Subjects
Cells, Cultured
Chemokine CCL8 - antagonists & inhibitors
Encephalitis, Viral - pathology
Gene Expression Regulation - immunology
HIV Infections - etiology
HIV Infections - genetics
HIV Infections - immunology
HIV-1 - pathogenicity
Humans
Inflammation - virology
Microglia - virology
MicroRNAs - genetics
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Summary:MicroRNA-mediated regulation of gene expression appears to be involved in a variety of cellular processes, including development, differentiation, proliferation, and apoptosis. Mir-146a is thought to be involved in the regulation of the innate immune response, and its expression is increased in tissues associated with chronic inflammation. Among the predicted gene targets for mir-146a, the chemokine CCL8/MCP-2 is a ligand for the CCR5 chemokine receptor and a potent inhibitor of CD4/CCR5-mediated HIV-1 entry and replication. In the present study, we have analyzed changes in the expression of mir-146a in primary human fetal microglial cells upon infection with HIV-1 and found increased expression of mir-146a. We further show that CCL8/MCP-2 is a target for mir-146a in HIV-1 infected microglia, as overexpression of mir-146a prevented HIV-induced secretion of MCP-2 chemokine. The clinical relevance of our findings was evaluated in HIV-encephalitis (HIVE) brain samples in which decreased levels of MCP-2 and increased levels of mir-146a were observed, suggesting a role for mir-146a in the maintenance of HIV-mediated chronic inflammation of the brain.--Rom, S., Rom, I., Passiatore, G., Pacifici, M., Radhakrishnan, S., Del Valle, L., Piña-Oviedo, S., Khalili, K., Eletto, D., Peruzzi, F. CCL8/MCP-2 is a target for mir-146a in HIV-1 infected human microglial cells.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.09-143503