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Regression of Peyer's patches in G alpha i2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis
Author(s): Ohman L, Franzen L, Rudolph U, Birnbaumer L, Hornquist EH
Source: GUT    Volume: 51    Issue: 3    Pages: 392-397    Published: SEP 2002  
Times Cited: 20     References: 46     
Abstract: Background: G protein deficient (Galphai2-/-) mice spontaneously develop an inflammatory bowel disease (IBD) closely resembling ulcerative colitis. Previous studies have demonstrated that gut T cells are hyperreactive to the endogenous microflora in most IBD models.

Aims: The aim of this study was to analyse Peyer's patches (PP), the inductive sites for gut mucosal immune responses.

Subjects and methods: Galphai2-/- mice, an animal model for IBD, were analysed using immunological methods with regard to phenotype and function.

Results: We found significantly decreased numbers of PP in Galphai2-/- mice. Even before the onset of colitis, Galphai2 deficient animals exhibited diminished size of PP, as judged by histology. This involution of PP was associated with strongly increased levels of apoptotic lymphocytes, associated with decreased levels of antiapoptotic intracellular protein Bcl-2. PP T lymphocytes showed highly elevated production of interferon gamma in response to the enteric flora compared with PP T cells from wild-type mice, which produced predominantly interleukin 10.

Conclusions: Thus even before the onset of colitis, the PP in Galphai2 deficient mice is a Th1 dominated milieu associated with downregulated levels of Bcl-2, resulting in increased apoptosis of lymphocytes leading to regression of PP. We speculate that this Th1 dominated microenvironment in the inductive site for mucosal immune responses contributes to the development of colitis in Galphai2 deficient mice.

Document Type: Article
Language: English
Reprint Address: Hornquist, EH (reprint author), Gothenburg Univ, Dept Clin Immunol, Guldhedsgatan 10, S-41346 Gothenburg, Sweden
Addresses:
1. Gothenburg Univ, Dept Clin Immunol, S-41346 Gothenburg, Sweden
2. Orebro Univ Hosp, Dept Pathol, Orebro, Sweden
3. Univ Zurich, Inst Pharmacol & Toxicol, Zurich, Switzerland
4. Univ Calif Los Angeles, Los Angeles, CA 90024 USA
Publisher: BRITISH MED JOURNAL PUBL GROUP, BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
Subject Category: Gastroenterology & Hepatology
IDS Number: 585DE
ISSN: 0017-5749
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