期刊
FASEB JOURNAL
卷 27, 期 1, 页码 243-254出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.12-217596
关键词
flagellin; inflammatory bowel disease; interleukin 10; epithelial cells
资金
- U.S. National Institutes of Health [DK079015]
- National Research Foundation (NRF) of Korea
- Ministry of Education, Science and Technology [2012R1A1A1042566]
- National Research Foundation of Korea [2012R1A1A1042566] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 mu g/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. FASEB J. 27, 243-254 (2013). www.fasebj.org
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据