title: HIV-1 Tat increases oxidant burden in the lungs of transgenic mice.
abstract: Chronic human immunodeficiency virus infection is associated with higher incidence of pulmonary complications including hypertension, vasculopathy, lymphocytic alveolitis, and interstitial pneumonitis not attributed to either opportunistic infections or presence of the virus. The Tat (transactivator of transcription) protein, a required transactivator for expression of full-length viral genes, is pleiotropic and influences expression of cellular inflammatory genes. Tat-dependent transactivation of cellular genes requires specific mediators, including NF-κB, widely recognized as sensitive to changes in cellular oxidant burden. We hypothesized that overproduction of Tat leads to increased oxidant burden and to alterations in basal inflammatory status as measured by NF-κB activation. We engineered transgenic mouse lines that express Tat (86-amino-acid isoform) in the lung under the control of the surfactant protein C promoter. Tat-transgenic mice exhibit increased pulmonary cellular infiltration, increased nitrotyrosine and carbonyl protein modifications, and increased levels of NF-κB, MnSOD, and thioredoxin-interacting protein. These data indicate that Tat increases oxidant burden and resets the threshold for inflammation, which may increase susceptibility to secondary injuries.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. adela.cota-gomez@ucdenver.edu
authors.forename: Adela
authors.initials: A
authors.lastname: Cota-Gomez
authors.forename: Ariana C
authors.initials: AC
authors.lastname: Flores
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Ling
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Flores
mesh_terms: D000818:Animals; D005260:Female; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism*; D018014:Gene Transfer Techniques; D015497:HIV-1; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D015696:Gene Products, tat; D016328:NF-kappa B