title: CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells.
abstract: 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.
authors.affiliation: Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, Philadelphia, PA 19122, USA.
authors.forename: Slava
authors.initials: S
authors.lastname: Rom
authors.forename: Inna
authors.initials: I
authors.lastname: Rom
authors.forename: Giovanni
authors.initials: G
authors.lastname: Passiatore
authors.forename: Marco
authors.initials: M
authors.lastname: Pacifici
authors.forename: Sujatha
authors.initials: S
authors.lastname: Radhakrishnan
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Sergio
authors.initials: S
authors.lastname: Piña-Oviedo
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Davide
authors.initials: D
authors.lastname: Eletto
authors.forename: Francesca
authors.initials: F
authors.lastname: Peruzzi
mesh_terms: D002478:Cells, Cultured; D054412:Chemokine CCL8 / Q000037:antagonists & inhibitors*; D018792:Encephalitis, Viral / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007249:Inflammation / Q000821:virology; D035683:MicroRNAs / Q000235:genetics*; D017628:Microglia / Q000821:virology*
chemical_list: D054412:Chemokine CCL8; C542542:MIRN146 microRNA, human; D035683:MicroRNAs