| PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment. | |
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MedLine Citation:
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PMID: 23038756 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Defective IL-10 allele is a risk factor for intestinal inflammation. Indeed, IL-10(-/-) mice are predisposed to spontaneous colitis in the presence of intestinal microbiota, indicating that microbial factors contribute to developing intestinal inflammation. By recognizing flagellin, TLR5 plays a quintessential role in microbial recognition in intestinal epithelial cells. Here, we treated flagellin (1.0 μg/mouse/d) in mouse colon and found that it elicited colonic inflammation in IL-10(-/-) mice, characterized with tissue hypertrophy, inflamed epithelium, and enhanced cytokine production in the colon (MPO, KC, IL-6; ≥2-fold; P < 0.05). These inflammatory effects were dramatically inhibited in TLR5(-/-);IL-10(-/-) mice. Intestinal epithelium specific PTEN deletion significantly attenuated flagellin-promoted colonic inflammation in IL-10(-/-) mice. As a molecular mechanism that PTEN deletion inhibited TLR5-elicited responses, we hypothesized that PTEN regulated TLR5-induced responses by controlling the involvement of Mal in TLR5 engagement. Mal interacted with TLR5 on flagellin, and Mal deficiency inhibited flagellin-induced responses in intestinal epithelial cells. Similarly, Mal(-/-);IL-10(-/-) mice showed reduced flagellin-promoted responses. Furthermore, PTEN deletion disrupted Mal-TLR5 interaction, resulting in diminished TLR5-induced responses. PTEN deletion impeded Mal localization at the plasma membrane and suppressed Mal-TLR5 interaction. These results suggest that, by controlling Mal recruitment, PTEN regulates TLR5-induced inflammatory responses. |
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Authors:
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Yoon Jeong Choi; Jane Jung; Hyo Kyun Chung; Eunok Im; Sang Hoon Rhee |
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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 Date: 2012-10-04 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 27 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-03 Completed Date: 2013-03-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 243-54 Citation Subset: IM |
Affiliation:
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Division of Digestive Diseases, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California 90095, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Intestines / metabolism, physiopathology* Membrane Glycoproteins / metabolism* Mice PTEN Phosphohydrolase / physiology* Real-Time Polymerase Chain Reaction Receptors, Interleukin-1 / metabolism* Signal Transduction Toll-Like Receptor 5 / metabolism, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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DK079015/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Glycoproteins; 0/Receptors, Interleukin-1; 0/TIRAP protein, mouse; 0/Toll-Like Receptor 5; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase |
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