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

• Published in: The 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
• Language: English
• 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
• DOI: 10.1096/fj.09-143503
• ISSN: 0892-6638

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.