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Inhibition of Adenosine Monophosphate‐activated Protein Kinase (AMPK) ameliorates the effects of Interferon gamma (IFN gamma) on epithelial barrier function in T84 cells
Author(s) -
Scharl Michael,
Barrett Kim E,
McCole Declan F
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.1189.10
Subject(s) - ampk , occludin , barrier function , protein kinase a , downregulation and upregulation , adenosine monophosphate , tight junction , chemistry , western blot , microbiology and biotechnology , amp activated protein kinase , adenosine , kinase , biology , biochemistry , gene
IFNγ plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Treatment of intestinal epithelial cells with IFNγ leads to decreased transepithelial resistance (TER), increased epithelial permeability and a downregulation of tight junction proteins. AMPK has been shown to reduce energy consuming processes during inflammation. Here, we investigated if AMPK is involved in IFNγ‐induced effects on epithelial barrier function. Protein analysis was performed by Western blot. TER was assessed by voltohmeter and confirmed with Ussing chambers. IFNγ increased AMPK phosphorylation in T84 cells (1000 U/ml, 6h). The AMPK inhibitor, Compound C (50 μM), reversed the IFNγ‐induced decrease in TER (p<0.001, n=5) across T84 monolayers at 72h treatment. In contrast, activation of AMPK with AICA‐Riboside‐5′‐Phosphate (1 mM, 24–72h) had no effect on TER. AMPK inhibition also prevented the IFNγ induced downregulation of the tight junction protein, occludin (p<0.05, n=3, 72h). In summary, these data show involvement of AMPK in IFNγ‐induced alterations in epithelial integrity. However, AMPK activity alone is not sufficient to generate such effects. These findings indicate a novel role for AMPK in the regulation of epithelial barrier function, and may have implications for inflammatory conditions associated with metabolic stress, such as IBD. Supported by the Crohn's and Colitis Foundation of America and NIH.