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Am J Physiol Gastrointest Liver Physiol (September 4, 2003). doi:10.1152/ajpgi.00227.2003
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Submitted on May 14, 2003
Accepted on August 30, 2003

Prolonged interferon-{gamma} exposure decreases ion transport, NKCC-1 and Na+, K+ ATPase expression in human intestinal xenografts in vivo

Lone S. Bertelsen1, Lars Eckmann1, and Kim E. Barrett1*

1 Department of Medicine, University of California, UCSD School of Medicine, San Diego, CA, USA

* To whom correspondence should be addressed. E-mail: kbarrett{at}ucsd.edu.

Interferon-{gamma} (IFN-{gamma}) is elevated in intestinal inflammation and alters barrier and transport functions in human colonic epithelial cell lines, but its effects on normal human small intestinal epithelium in vivo are poorly defined. We investigated effects of prolonged IFN-{gamma} exposure on ion transport and expression of transporters using human fetal small intestinal xenografts. Xenograft-bearing mice were injected with IFN-{gamma}, and 24 hours later, xenografts were harvested and mounted in Ussing chambers. Baseline potential difference was not affected by IFN-{gamma} treatment. However, conductance was enhanced, and agonist-stimulated ion transport was decreased. IFN-{gamma} also decreased expression of the Na+/K+/2Cl- co-transporter and the alpha-subunit of Na+,K+ ATPase compared to controls, whereas levels of the chloride channels CLCA and CFTR were unaltered. Thus, prolonged exposure to IFN-{gamma} leads to decreased ion secretion, due, in part, to decreased ion transporter levels. These findings demonstrate the implications of elevated IFN-{gamma} levels in human small intestine and validate the human intestinal xenograft as a model to study chronic effects of physiologically relevant stimuli.




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