| First Author | Wu D | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 15 | Pages | 13357-69 |
| PubMed ID | 21303908 | Mgi Jnum | J:171142 |
| Mgi Id | MGI:4948788 | Doi | 10.1074/jbc.M110.214965 |
| Citation | Wu D, et al. (2011) Interleukin-13 (IL-13)/IL-13 Receptor {alpha}1 (IL-13R{alpha}1) Signaling Regulates Intestinal Epithelial Cystic Fibrosis Transmembrane Conductance Regulator Channel-dependent Cl- Secretion. J Biol Chem 286(15):13357-69 |
| abstractText | 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/Il13ralpha1(-/-), iIL-13Tg/Il13ralpha2(-/-), and iIL-13Tg/Stat6(-/-) mice revealed that IL-13-mediated dysregulation of epithelial architecture and Cl(-) conductance is dependent on IL-13Ralpha1 and STAT-6. These observations demonstrate a central role for the IL-13/IL-13Ralpha1 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. |
