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.
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.
Schnoor
M
M
Epithelial Pathobiology Unit, Department for Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Betanzos
A
A
Weber
D A
DA
Parkos
C A
CA
D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D003106:Colon / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D019108:Tight Junctions / Q000378:metabolism*
C490287:GBP1 protein, human; D034741:RNA, Small Interfering; D007371:Interferon-gamma; D019204:GTP-Binding Proteins