Document Detail


PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment.
MedLine Citation:
PMID:  23038756     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yoon Jeong Choi; Jane Jung; Hyo Kyun Chung; Eunok Im; Sang Hoon Rhee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-04
Journal Detail:
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:
Created Date:  2013-01-03     Completed Date:  2013-03-07     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  243-54     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
DK079015/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

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