title: Antiretroviral agents increase NO production in gp120/IFNγ-stimulated cultures of rat microglia via an arginase-dependent mechanism.
abstract: In the present study we carried out a screening of different Antiretroviral drugs (ARVs) for their potential pro-inflammatory effects on microglial cells. Efavirenz, neviparine, darunavir and atazanavir increased nitric oxide (NO) production in microglial cells activated with Gp120CN54 and interferon-γ. The stimulatory effect on NO production appeared to be mediated by inhibition of arginase (ARG) I activity. Consistently the ARG inhibitor, Nω-hydroxy-nor-arginine, mimicked the effects of ARVs. Take together these data suggest that ARG is an additional molecular target of different ARVs, whose inhibition can contribute to their pharmacological activity as well as explain the neurotoxic potential.
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, 00168, Rome, Italy. Electronic address: lucia.lisi@rm.unicatt.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lisi
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, 00168, Rome, Italy. Electronic address: antonella.tramutola@gmail.com.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tramutola
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, 00168, Rome, Italy. Electronic address: pnavarra@rm.unicatt.it.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, 00168, Rome, Italy. Electronic address: cinzia.dellorusso@rm.unicatt.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dello Russo
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D001119:Arginase / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: C110400:2',7'-dichlorodihydrofluorescein diacetate; D044966:Anti-Retroviral Agents; D039481:CD11b Antigen; D016207:Cytokines; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D015699:HIV Envelope Protein gp120; D016898:Interferon-alpha; D011458:Prostaglandins E; D009569:Nitric Oxide; D001119:Arginase; D019331:NG-Nitroarginine Methyl Ester
keywords: Antiretroviral drugs; Arginase; HIV; Microglia; NO; Urea