Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages: Implications for impaired immune function during disease

James Haorah, David Heilman, Casey Diekmann, Natalia Osna, Terrence M. Donohue, Anuja Ghorpade, Yuri Persidsky

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Proteasomes (proteinase complexes, PR) and immunoproteasomes (IPR) degrade damaged proteins and affect protein processing required for antigen presentation by mononuclear phagocytes. These critical immune processes are attenuated during progressive HIV-1 infection and are affected by alcohol abuse. To investigate the mechanisms underlying these functional changes, we measured PR and CYP2E1 activities [an ethanol (EtOH) metabolizing enzyme] and reactive oxygen species (ROS) in human monocyte-derived macrophages (MDM) following HIV-1 infection and EtOH treatment. We observed progressive declines of PR activity and PR/IPR contents in HIV-1-infected MDM. PR activity and IPR expression increased after IFN-γ stimulation but reduced after HIV-1 infection. EtOH inhibited both IFN-γ-induced PR and IPR. Paradoxically, EtOH attenuated PR catalytic activity in infected MDM and suppressed viral replication. Elevated ROS followed EtOH exposure and paralleled decreased PR activity. The latter was restored by anti-oxidant. The data support the notion that HIV-1 infection and EtOH may work in concert to affect immune function including antigen presentation and thereby affect disease progression.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalCellular Immunology
Volume229
Issue number2
DOIs
StatePublished - Jun 1 2004

Fingerprint

HIV Protease
HIV-1
Macrophages
Alcohols
HIV Infections
Antigen Presentation
Reactive Oxygen Species
Cytochrome P-450 CYP2E1
Phagocytes
Oxidants
Alcoholism
Disease Progression
Proteins
Peptide Hydrolases
Ethanol
Enzymes

Keywords

  • Antigen presentation
  • CYP2E1
  • Mononuclear phagocytes
  • Reactive oxygen species

ASJC Scopus subject areas

  • Immunology

Cite this

Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages : Implications for impaired immune function during disease. / Haorah, James; Heilman, David; Diekmann, Casey; Osna, Natalia; Donohue, Terrence M.; Ghorpade, Anuja; Persidsky, Yuri.

In: Cellular Immunology, Vol. 229, No. 2, 01.06.2004, p. 139-148.

Research output: Contribution to journalArticle

Haorah, James ; Heilman, David ; Diekmann, Casey ; Osna, Natalia ; Donohue, Terrence M. ; Ghorpade, Anuja ; Persidsky, Yuri. / Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages : Implications for impaired immune function during disease. In: Cellular Immunology. 2004 ; Vol. 229, No. 2. pp. 139-148.
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