Proinflammatory synergism of ethanol and HIV-1 Tat protein in brain tissue

Flora, Govinder; Peng, Hong; Lee, Yong Woo; Ravikumar, R.; Nath, Avindra; Hennig, Bernhard; Toborek, Michał

doi:10.1016/j.expneurol.2004.06.007

Cited by 51 publications

(51 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…9 HIV-1 proteins and ethanol appear to produce synergistic neurotoxic effects. 23,63 Our data indicates that chronic ethanol administration enhances microglial reaction more than three times as compared to one caused by HIV-1-infected MDMs alone. Augmentation of neuroinflammation because of CTL infiltration further amplified microglial reaction suggesting the concerted effects of both factors promote neuronal demise.…”

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

Alcohol Abuse Enhances Neuroinflammation and Impairs Immune Responses in an Animal Model of Human Immunodeficiency Virus-1 Encephalitis

Potula

Haorah

Knipe

et al. 2006

The American Journal of Pathology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 79%

“…23 The degree of nitrotyrosine expression provides an index of the production of reactive nitrogen species and potential cell damage throughout a period of time. Nitrotyrosine analysis was performed by Western blot analysis on protein extracts from brain tissue of ethanol and control mice.…”

Section: Chronic Ethanol Exposure Induces Neuroinflammation and Oxidamentioning

confidence: 99%

Alcohol Abuse Enhances Neuroinflammation and Impairs Immune Responses in an Animal Model of Human Immunodeficiency Virus-1 Encephalitis

Potula

Haorah

Knipe

et al. 2006

The American Journal of Pathology

View full text Add to dashboard Cite

“…Other studies suggest that the basic region and the C-terminal region of Tat seem not to be involved in the production of TNF-α (New et al, 1998). Recently, HIV-1 Tat 1-72 lacking residues 31-61, where the basic region is located, has been used as a control peptide for the neurotoxic actions of Tat 1-72 (Gurwell et al, 2001;Prendergast et al, 2002;Aksenov et al, 2003;Toborek et al, 2003;Self et al, 2004a;Flora et al, 2005;Perry et al, 2005). In preliminary studies, we noted that Tat Δ31-61 increased markedly the production of TNF-α by differentiated U937 cells, providing us with a tool to explore Tat's ability to indirectly affect neuronal viability.…”

Section: Introductionmentioning

confidence: 99%

Human immunodeficiency virus type-1 protein Tat induces tumor necrosis factor-α-mediated neurotoxicity

Buscemi

Ramonet

Geiger

2007

Neurobiology of Disease

View full text Add to dashboard Cite

HIV-1 infection causes, with increasing prevalence, neurological disorders characterized in part by neuronal cell death. The HIV-1 protein Tat has been shown to be directly and indirectly neurotoxic. Here, we tested the hypothesis that a non-neurotoxic epitope of Tat can, through actions on immune cells, increase neuronal cell death. Tat 1-72 and a mutant Tat 1-72 lacking the neurotoxic epitope (Tat Δ31-61 ) concentration-dependently and markedly increased TNF-α production in macrophagelike differentiated human U937 and THP-1 cells, in mouse peritoneal macrophages and in mouse brain microglia. Tat 1-72 was but Tat Δ31-61 was not neurotoxic when applied directly to neurons. Supernatants from U937 cells treated with either Tat 1-72 or Tat Δ31-61 were neurotoxic and their immunoneutralization with an anti-TNF-α antibody decreased Tat 1-72 -and Tat Δ31-61 -induced neurotoxicity. Together, these results demonstrate that the neurotoxic epitope of Tat 1-72 is different from the epitope that is indirectly neurotoxic following production of TNF-α from immune cells, and suggest that therapeutic interventions against TNF-α might be beneficial against HIV-1 associated neurological disorders.

show abstract

“…Além disso, em um recente estudo longitudinal, o consumo pesado de álcool foi associado com reduzida adesão aos ARVs, fibrose hepática, aumento da carga viral do HIV e redução de linfócitos CD4+ 100 . No cenário cerebral, há evidências de um contexto de relações bioquímicas entre os efeitos do álcool e a infecção pelo HIV, como observado previamente em modelos experimentais de roedores 101,102 . O álcool interage com a proteína HIV-1 Tat (Trans-Activator of Transcription) e isto resulta em um sinergismo para secreções de neurotransmissores (incluindo dopamina e glutamato), fatores apoptóticos e citocinas pró-inflamatórias cerebrais [102][103][104] .…”

unclassified

“…No cenário cerebral, há evidências de um contexto de relações bioquímicas entre os efeitos do álcool e a infecção pelo HIV, como observado previamente em modelos experimentais de roedores 101,102 . O álcool interage com a proteína HIV-1 Tat (Trans-Activator of Transcription) e isto resulta em um sinergismo para secreções de neurotransmissores (incluindo dopamina e glutamato), fatores apoptóticos e citocinas pró-inflamatórias cerebrais [102][103][104] . Mesmo com a adesão e eficiência dos ARVs, a proteína Tat pode persistir no organismo e pode reforçar os efeitos lesivos do álcool 105 .…”

unclassified