TLR2 and interleukin-1 0 are involved in Bacteroides fragilis-mediated prevention of DSS-induced colitis in gnotobiotic mice

被引:81
作者
Chang, Yi-Chih [1 ]
Ching, Yung-Hao [2 ]
Chiu, Chien-Chao [3 ]
Liu, Ju-Yun [4 ]
Hung, Shao-Wen [3 ]
Huang, Wen-Ching [5 ]
Huang, Yen-Te [4 ]
Chuang, Hsiao-Li [4 ]
机构
[1] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan
[2] Tzu Chi Univ, Dept Mol Biol & Human Genet, Hualien, Taiwan
[3] Agr Technol Res Inst, Div Anim Resources, Anim Technol Labs, Hsinchu, Taiwan
[4] Natl Lab Anim Ctr, Natl Appl Res Labs, Taipei, Taiwan
[5] Natl Taipei Univ Nursing & Hlth Sci, Dept Exercise & Hlth Sci, Taipei, Taiwan
来源
PLOS ONE | 2017年 / 12卷 / 07期
关键词
NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTORS; INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; COMMENSAL; DISEASE; PATHOGENESIS; EXPRESSION; ATTENUATE; MUCOSA;
D O I
10.1371/journal.pone.0180025
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background and aims Bacteroides fragilis (BF) are Gram-negative anaerobe symbionts present in the colon. Recent studies have reported the beneficial role of BF in maintaining intestinal homeostasis, stimulating host immunologic development, and preventing infectious colitis caused by pathogenic bacteria. Our previous studies showed that monocolonization of germ-free mice with BFsignificantly reduced colon inflammations and damage. Methods In order to investigate the Toll-like receptor-2 (TLR2), TLR4, and interleukin 10 (IL-10) molecular signaling pathways involved in BF -mediated prevention of dextran sulfate sodium (DSS)-induced colitis. The wild -type (WT), TLR4, TLR2, and IL -10 knockout (-/-) germ -free mice grown were with or without BFcolonization for 28 days, and then administered 1% DSS in drinking water for 7 day to induce acute ulcerative colitis. Results We compared phenotypes such as weight loss, disease activity, intestinal histological scores, and immunohistochemistry for inflammatory cells. Unlike WT and TLR4(-/-) mice, the severity of DSS-colitis did not improve in TLR2(-/-) animals after BFcolonization. The BF enhanced anti-inflammatory cytokines IL -10 expression and inhibited pro -inflammatory related tumor necrosis factor (TNF-alpha) and IL-6 mRNA expression in both WT and TLR4(-/-) mice. In contrast, the failed to up-regulated IL -10 and down -regulated the TNF-a and IL-6 in BFcolonization TLR2-/- mice. In addition, we further perform IL -104- mice to clarify whether the BF through TLR2/IL -10 pathway to alleviate DSS-colitis. There were no significant differences in colitis severity and pro -inflammatory related genes expression in the IL -10-/mice with or without BFcolonization. Conclusions These results indicate the disease-preventing effects of BF in acute DSS-induced colitis may occur through the TLR2/IL-10 signal pathway.
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页数:16
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共 37 条
[1]  
[Anonymous], 2010, J VIS EXP, DOI DOI 10.3791/1652
[2]   Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation:: Evidence in Crohn disease and experimental colitis in vivo [J].
Atreya, R ;
Mudter, J ;
Finotto, S ;
Müllberg, J ;
Jostock, T ;
Wirtz, S ;
Schütz, M ;
Bartsch, B ;
Holtmann, M ;
Becker, C ;
Strand, D ;
Czaja, J ;
Schlaak, JF ;
Lehr, HA ;
Autschbach, F ;
Schürmann, G ;
Nishimoto, N ;
Yoshizaki, K ;
Ito, H ;
Kishimoto, T ;
Galle, PR ;
Rose-John, S ;
Neurath, MF .
NATURE MEDICINE, 2000, 6 (05) :583-588
[3]   Anti-inflammatory effects of probiotic yogurt in inflammatory bowel disease patients [J].
Baroja, M. Lorea ;
Kirjavainen, P. V. ;
Hekmat, S. ;
Reid, G. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2007, 149 (03) :470-479
[4]   Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease [J].
Basso, P. J. ;
Fonseca, M. T. C. ;
Bonfa, G. ;
Alves, V. B. F. ;
Sales-Campos, H. ;
Nardini, V. ;
Cardoso, C. R. B. .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 2014, 47 (09) :727-737
[5]   Increased mucosal tumour necrosis factor α production in Crohn's disease can be downregulated ex vivo by probiotic bacteria [J].
Borruel, N ;
Carol, M ;
Casellas, F ;
Antolín, M ;
de Lara, F ;
Espín, E ;
Naval, J ;
Guarner, F ;
Malagelada, JR .
GUT, 2002, 51 (05) :659-664
[6]   Toll-Like Receptor 2 Regulates Intestinal Inflammation by Controlling Integrity of the Enteric Nervous System [J].
Brun, Paola ;
Giron, Maria Cecilia ;
Qesari, Marsela ;
Porzionato, Andrea ;
Caputi, Valentina ;
Zoppellaro, Chiara ;
Banzato, Serena ;
Grillo, Alessia Rosaria ;
Spagnol, Lisa ;
De Caro, Raffaele ;
Pizzuti, Daniela ;
Barbieri, Vito ;
Rosato, Antonio ;
Sturniolo, Giacomo Carlo ;
Martines, Diego ;
Zaninotto, Giovanni ;
Palu, Giorgio ;
Castagliuolo, Ignazio .
GASTROENTEROLOGY, 2013, 145 (06) :1323-1333
[7]   Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function [J].
Cario, E. ;
Gerken, G. ;
Podolsky, D. K. .
GASTROENTEROLOGY, 2007, 132 (04) :1359-1374
[8]   Monocolonization of Germ-Free Mice with Bacteroides fragilis Protects against Dextran Sulfate Sodium-Induced Acute Colitis [J].
Chiu, Chien-Chao ;
Ching, Yung-Hao ;
Wang, Yu-Chih ;
Liu, Ju-Yun ;
Li, Yen-Peng ;
Huang, Yen-Te ;
Chuang, Hsiao-Li .
BIOMED RESEARCH INTERNATIONAL, 2014, 2014
[9]   Toll-like receptor 2 monoclonal antibody or/and Toll-like receptor 4 monoclonal antibody increase counts of Lactobacilli and Bifidobacteria in dextran sulfate sodium-induced colitis in mice [J].
Dong, Le ;
Li, Juan ;
Liu, Yi ;
Yue, Wenjie ;
Luo, Xiaoting .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2012, 27 (01) :110-119
[10]   Expression of Toll-like receptors in the mucosa of patients with ulcerative colitis [J].
Fan, Yujing ;
Liu, Bingrong .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2015, 9 (04) :1455-1459