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Interleukin‐13 (IL‐13)/IL‐13 receptor α1 (IL‐13R α1) signaling regulates intestinal epithelial Cystic fibrosis transmembrane conductance regulator (CFTR) channel‐dependent Cl − secretion
Author(s) -
Wu David Xiao Yang,
Ahrens Richard,
Osterfeld Heather,
Groschwitz Katherine,
Foster Paul,
Rothenberg Marc E,
Matthaei Klaus I.,
Finkelman Fred D.,
Hogan Simon P
Publication year - 2011
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.25.1_supplement.561.16
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 CFTR expression and activity. Generation of iIL‐13Tg/IL13Rα1−/− and iIL‐13Tg/IL13Rα2−/− mice revealed that IL‐13‐ mediated dysregulation of epithelial architecture and Cl − conductance is dependent on IL‐13Rα1. These observations demonstrate a central role for the IL‐13/IL‐13Rα1 pathway in the regulation of intestinal epithelial cell Cl − secretion via upregulation of CFTR, suggesting an important role for this pathway in secretory diarrhea.