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PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment
- Source :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 27(1)
- Publication Year :
- 2012
-
Abstract
- 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.—Choi, Y. J., Jung, J., Chung, H. K., Im, E., Rhee, S. H. PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment.
- Subjects :
- TIRAP
medicine.medical_treatment
Inflammation
Biology
Real-Time Polymerase Chain Reaction
Biochemistry
Research Communications
Mice
Genetics
medicine
PTEN
Animals
Colitis
Intestinal Mucosa
Molecular Biology
Membrane Glycoproteins
PTEN Phosphohydrolase
Receptors, Interleukin-1
medicine.disease
Intestinal epithelium
Intestines
Toll-Like Receptor 5
Cytokine
TLR5
Cancer research
biology.protein
medicine.symptom
Flagellin
Biotechnology
Signal Transduction
Subjects
Details
- ISSN :
- 15306860
- Volume :
- 27
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Accession number :
- edsair.doi.dedup.....f7554a2d1d53fd83209aa340fd00ab3a