| Interleukin-13 (IL-13)/IL-13 receptor alpha1 (IL-13Ralpha1) signaling regulates intestinal epithelial cystic fibrosis transmembrane conductance regulator channel-dependent Cl- secretion. | |
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MedLine Citation:
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PMID: 21303908 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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David Wu; Richard Ahrens; Heather Osterfeld; Taeko K Noah; Katherine Groschwitz; Paul S Foster; Kris A Steinbrecher; Marc E Rothenberg; Noah F Shroyer; Klaus I Matthaei; Fred D Finkelman; Simon P Hogan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-02-08 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-11 Completed Date: 2011-06-28 Revised Date: 2012-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 13357-69 Citation Subset: IM |
Affiliation:
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Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Caco-2 Cells Chlorides / metabolism* Cystic Fibrosis Transmembrane Conductance Regulator / genetics, metabolism* Cysts / genetics, metabolism, pathology Diarrhea / genetics, metabolism, pathology Fibrosis Humans Interleukin-13 / genetics, metabolism* Interleukin-13 Receptor alpha1 Subunit / genetics, metabolism* Intestinal Diseases / genetics, metabolism*, pathology Intestinal Mucosa / metabolism*, pathology Ion Transport / genetics Mice Mice, Inbred BALB C Mice, Knockout STAT6 Transcription Factor / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA142826-01/CA/NCI NIH HHS; R01AI073553-01/AI/NIAID NIH HHS; R03 DK084167-01/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chlorides; 0/Il13ra1 protein, mouse; 0/Interleukin-13; 0/Interleukin-13 Receptor alpha1 Subunit; 0/STAT6 Transcription Factor; 0/Stat6 protein, mouse; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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