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PMID:19079332

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Citation

Schnoor, M, Betanzos, A, Weber, DA and Parkos, CA (2009) Guanylate-binding protein-1 is expressed at tight junctions of intestinal epithelial cells in response to interferon-gamma and regulates barrier function through effects on apoptosis. Mucosal Immunol 2:33-42

Abstract

Guanylate-binding protein-1 (GBP-1) is an interferon inducible large GTPase involved in endothelial cell proliferation and invasion. In this report, expression and function of GBP-1 were investigated in vitro in intestinal epithelia after exposure to interferon-gamma and in human colonic mucosa from individuals with inflammatory bowel disease (IBD). Interestingly, in contrast to other epithelia, GBP-1 distributed to the plasma membrane in intestinal epithelial cells where it colocalized with the tight junction protein coxsackie- and adenovirus receptor. In addition, expression of GBP-1 was upregulated in colonic epithelia of individuals with IBD. Downregulation of GBP-1 by siRNA resulted in enhanced permeability that correlated with increased apoptosis. Indeed, inhibition of caspase activity prevented the inhibition of barrier formation induced by the loss of GBP-1. These data suggest that GBP-1 is a novel marker of intestinal mucosal inflammation that may protect against epithelial apoptosis induced by inflammatory cytokines and subsequent loss of barrier function.

Links

PubMed PMC2877263 Online version:10.1038/mi.2008.62

Keywords

Apoptosis/drug effects; Apoptosis/immunology; Cell Line; Colon/immunology; Colon/metabolism; Down-Regulation/drug effects; Epithelial Cells/immunology; Epithelial Cells/metabolism; GTP-Binding Proteins/genetics; GTP-Binding Proteins/metabolism; Humans; Inflammatory Bowel Diseases/genetics; Inflammatory Bowel Diseases/immunology; Inflammatory Bowel Diseases/metabolism; Interferon-gamma/pharmacology; Intestinal Mucosa/immunology; Intestinal Mucosa/metabolism; RNA, Small Interfering/genetics; Tight Junctions/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GBP1

GO:0005923: tight junction

ECO:0000314:

C

Figure 2B. An IF was done in human epithelial cells. GBP1 was detected in the tight junctions colocalizing with CAR.

complete


See also

References

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