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

doi:10.1016/j.cellimm.2004.07.005

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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

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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-gamma stimulation but reduced after HIV-1 infection. EtOH inhibited both IFN-gamma-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.

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Alcoholism Blotting, Western Cysteine Endopeptidases Cytochrome P-450 CYP2E1 Fluorometry HIV Infections HIV-1 Humans Interferon-gamma Lymphocyte Activation Macrophages Proteasome Endopeptidase Complex Reactive Oxygen Species Virus Replication Journal Article Research Support, U.S. Gov't, P.H.S.

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James Haorah, David Heilman, Casey Diekmann, Natalia Osna, Terrence M Donohue, Anuja Ghorpade, Yuri Persidsky. 2004. Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages: implications for impaired immune function during disease.. https://doi.org/10.1016/j.cellimm.2004.07.005

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