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Expression of the Crohn's disease candidate gene, PTPN2, is upregulated in active Crohn's disease
Author(s) -
Scharl Michael,
Weber Achim,
Hausmann Martin,
Rogler Gerhard,
McCole Declan F
Publication year - 2010
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.24.1_supplement.998.4
Subject(s) - lamina propria , immunostaining , crohn's disease , medicine , biopsy , inflammatory bowel disease , pathology , cytokine , ileum , gene expression , immunology , immunohistochemistry , gastroenterology , disease , epithelium , biology , gene , biochemistry
We have recently shown that IFNγ, a major cytokine involved in Crohn's disease (CD), increases expression and activity of the CD candidate gene, PTPN2, in intestinal epithelial cells (IEC). We have also shown that PTPN2 restricts IFNγ‐induced IEC permeability. Here, we investigated whether PTPN2 expression is altered in active CD. mRNA analysis was performed by real‐time PCR. Immunostaining was performed on formalin‐fixed mucosal biopsies. We investigated PTPN2 mRNA levels in biopsies from macroscopically non‐inflamed areas of the terminal ileum, colon or rectum of CD patients in clinical and macroscopic remission; macroscopically inflamed areas of the terminal ileum and colon of CD patients with clinically active disease; or healthy control subjects undergoing routine screening. We observed significantly elevated PTPN2 mRNA in active CD (p<0.05; n=9), but not in CD patients in remission. Immunostaining showed elevated epithelial and lamina propria PTPN2 in CD vs. controls. CD patients with active disease, but not those in remission, also showed an approximately three‐fold increase in tissue IFNγ mRNA levels compared to healthy controls. H&E‐stained biopsy specimens indicated acute inflammation in patients with active CD only. Overall, our findings demonstrate altered PTPN2 expression in active CD and correlate with observed effects of IFNγ on PTPN2 expression in vitro . Supported by the CCFA and DFG.