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Guanylate binding protein‐1 (GBP‐1) is upregulated in intestinal epithelia under inflammatory conditions, localizes to tight junctions and regulates epithelial barrier function
Author(s) -
Schnoor Michael,
Betanzos Abigail,
Parkos Charles
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.328.4
Subject(s) - tight junction , downregulation and upregulation , barrier function , epithelium , microbiology and biotechnology , apoptosis , inflammatory bowel disease , immunofluorescence , intestinal mucosa , occludin , intestinal epithelium , chemistry , biology , immunology , pathology , medicine , antibody , gene , biochemistry , genetics , disease
GBP‐1 belongs to the family of large GTPases, is strongly induced in leukocytes and endothelial cells after IFN‐γ treatment and regulates endothelial cell proliferation under inflammatory conditions. Given the dependence of GBP‐1 expression on IFN‐γ, and the elevated level of IFN‐γ within intestinal mucosa of individuals with inflammatory bowel disease (IBD), we investigated whether GBP‐1 is expressed in colonic epithelial cells. Analyses of different epithelial cell lines revealed that GBP‐1 expression was low to absent in all cells tested under resting conditions, but was strongly induced in all tested epithelial cell lines after IFN‐γ treatment. Localization studies revealed that GBP‐1 is expressed at the plasma membrane and colocalized with the tight junction protein coxsackie‐ and adenovirus receptor (CAR) only in colonic epithelial cells. Immunofluorescence labeling of human colonic mucosa revealed upregulation of GBP‐1 expression in the epithelium of individuals with active IBD. Intriguingly, colocalization of GBP‐1 with CAR was also observed in IBD patients. Functional studies employing siRNA‐mediated knock down of GBP‐1 in colonic epithelia demonstrated delayed epithelial barrier formation and increased susceptibility to apoptosis. These data suggest that GBP‐1 expression in colonic epithelia may play a role in regulation of the epithelial barrier under inflammatory conditions.