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Inflammation and epithelial cell injury in AIDS enteropathy: involvement of endoplasmic reticulum stress.

Authors: Maingat, F  Halloran, B  Acharjee, S  Van Marle, G  Church, D  Gill, MJ  Uwiera, RR  Cohen, EA  Meddings, J  Madsen, K  Power, C 
Citation: Maingat F, etal., FASEB J. 2011 Jul;25(7):2211-20. Epub 2011 Mar 22.
Pubmed: (View Article at PubMed) PMID:21427211
DOI: Full-text: DOI:10.1096/fj.10-175992

Immunosuppressive lentivirus infections, including human, simian, and feline immunodeficiency viruses (HIV, SIV, and FIV, respectively), cause the acquired immunodeficiency syndrome (AIDS), frequently associated with AIDS enteropathy. Herein, we investigated the extent to which lentivirus infections affected mucosal integrity and intestinal permeability in conjunction with immune responses and activation of endoplasmic reticulum (ER) stress pathways. Duodenal biopsies from individuals with HIV/AIDS exhibited induction of IL-1beta, CD3epsilon, HLA-DRA, spliced XBP-1(Xbp-1s), and CHOP expression compared to uninfected persons (P<0.05). Gut epithelial cells exposed to HIV-1 Vpr demonstrated elevated TNF-alpha, IL-1beta, spliced Xbp-1s, and CHOP expression (P<0.05) together with calcium activation and disruption of epithelial cell monolayer permeability. In addition to reduced blood CD4(+) T lymphocyte levels, viral loads in the gut and plasma were high in FIV-infected animals (P<0.05). FIV-infected animals also exhibited a failure to gain weight and increased lactulose/mannitol ratios compared with uninfected animals (P<0.05). Proinflammatory and ER stress gene expression were activated in the ileum of FIV-infected animals (P<0.05), accompanied by intestinal epithelial damage with loss of epithelial cells and leukocyte infiltration of the lamina propria. Lentivirus infections cause gut inflammation and ensuing damage to intestinal epithelial cells, likely through induction of ER stress pathways, resulting in disruption of gut functional integrity.


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RGD Object Information
RGD ID: 5490157
Created: 2011-09-06
Species: All species
Last Modified: 2011-09-06
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.