Ethanol enhances TNF-alpha-inducible NF kappa B activation and HIV-1-LTR transcription in CD4+jurkat T lymphocytes

Citation
Q. Dong et al., Ethanol enhances TNF-alpha-inducible NF kappa B activation and HIV-1-LTR transcription in CD4+jurkat T lymphocytes, J LA CL MED, 136(5), 2000, pp. 333-343
Citations number
86
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
ISSN journal
0022-2143 → ACNP
Volume
136
Issue
5
Year of publication
2000
Pages
333 - 343
Database
ISI
SICI code
0022-2143(200011)136:5<333:EETNKB>2.0.ZU;2-A
Abstract
During the latent phase of human immunodeficiency virus type 1 (HIV-1) infe ction, CD4(+) T cells carrying replication-competent proviral HIV-1 DNA pla y an important role in persistence of the virus. Several cofactors can indu ce and or amplify HIV-1 replication and negatively affect disease progressi on and pathogenesis. alpha Ethanol consumption is an important risk factor for HIV-1 infection, and it has been implicated in increased HIV-1 replicat ion and progression of infection. Because tumor necrosis factor-alpha (TNF- alpha) is an important modulator of HIV-1 replication, in the present study we examined the possible effects of ethanol on TNF-alpha -inducible signal ing associated with HIV-1 replication in human CD4+ T cells (Jurkat E6-1). We demonstrate that clinically relevant ethanol concentrations significantl y potentiate TNF-alpha -inducible NF kappaB, Although ethanol effectively c ollaborated with TNF-alpha, by itself it did not have a direct effect on NF kappaB activation. The ethanol-dependent potentiation of TNF-alpha -induci ble NF kappaB nuclear translocation was observed to involve the enhanced de gradation of I kappaB alpha. Additionally, the ethanol-mediated potentiatio n of TNF-alpha -inducible NF kappaB activation was abrogated by the known a ntioxidant pyrrolidinedithiocarbamate, suggesting an important mechanistic role for reactive oxygen species in this process. In correspondence with it s effect on NF kappaB, ethanol was also observed to significantly enhance H IV-1 long terminal repeat-dependent transcription induced by TNF-alpha. Ove rall, the data provide a molecular basis for the possible role of ethanol a s a cofactor that can adversely affect HIV-1 infection and pathogenesis.