- Title
- Interleukin-13 (IL-13)/IL-13 receptor α1 (IL-13Rα1) signaling regulates intestinal epithelial cystic fibrosis transmembrane conductance regulator channel-dependent Cl− secretion
- Creator
- Wu, David; Ahrens, Richard; Finkelman, Fred D.; Hogan, Simon P.; Osterfeld, Heather; Noah, Taeko K.; Groschwitz, Katherine; Foster, Paul S.; Steinbrecher, Kris A.; Rothenberg, Marc E.; Shroyer, Noah F.; Matthaei, Klaus I.
- Relation
- Journal of Biological Chemistry Vol. 286, Issue 15, p. 13357-13369
- Publisher Link
- http://dx.doi.org/10.1074/jbc.M110.214965
- Publisher
- American Society for Biochemistry and Molecular Biology
- Resource Type
- journal article
- Date
- 2011
- Description
- Interleukin-13 (IL-13) has been linked to the pathogenesis of inflammatory diseases of the gastrointestinal tract. It is postulated that IL-13 drives inflammatory lesions through the modulation of both hematopoietic and nonhematopoietic cell function in the intestine. To delineate the relevant contribution of elevated levels of intestinal IL-13 to intestinal structure and function, we generated an intestinal IL-13 transgenic mouse (iIL-13Tg). We show that constitutive overexpression of IL-13 in the small bowel induces modification of intestinal epithelial architecture (villus blunting, goblet cell hyperplasia, and increased epithelial proliferation) and epithelial function (altered basolateral → apical Cl− ion conductance). Pharmacological analyses in vitro and in vivo determined that elevated Cl− conductance is mediated by altered cystic fibrosis transmembrane conductance regulator expression and activity. Generation of iIL-13Tg/Il13rα1−/−, iIL-13Tg/Il13rα2−/−, and iIL-13Tg/Stat6−/− mice revealed that IL-13-mediated dysregulation of epithelial architecture and Cl− conductance is dependent on IL-13Rα1 and STAT-6. These observations demonstrate a central role for the IL-13/IL-13Rα1 pathway in the regulation of intestinal epithelial cell Cl− secretion via up-regulation of cystic fibrosis transmembrane conductance regulator, suggesting an important role for this pathway in secretory diarrhea.
- Subject
- interleukin 13; inflammatory diseases; gastrointestinal tract; intestines
- Identifier
- http://hdl.handle.net/1959.13/1065081
- Identifier
- uon:17727
- Identifier
- ISSN:0021-9258
- Language
- eng
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