title: 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.
abstract: OBJECTIVE
  The accurate pathogenesis of ulcerative colitis (UC) is not yet well understood. Recently, Toll-like receptor 2 (TLR2), TLR4 and gut microbial flora have been proved as playing important roles in the process of UC. This study was to evaluate the effect of TLR2 and TLR4 monoclonal antibodies on gut microbial flora in dextran sulfate sodium (DSS)-induced colitis in a mouse model.
  
  
  METHODS
  We evaluated the effects of the TLR2 and TLR4 monoclonal antibodies on the development of DSS-induced colitis. Clinical symptoms were evaluated by the disease activity index (DAI), while tissue samples were evaluated by histological scoring (HS). Meanwhile, the mucosal mRNA expressions of TLR2, TLR4, interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-17 were analyzed by Realtime polymerase chain reaction (PCR). The mucosal protein TRAF6, TAB1, P-IKK, P-P38α mitogen-activated protein kinase (MAPL) and c-jun expressions of the TLR2 and TLR4 signaling pathways were analyzed using Western blot. The mucosal nuclear factor kappa B (NF-κB) was analyzed using electrophoretic mobility shift assay. Fecal samples were obtained directly from the cecum for microbiological studies.
  
  
  RESULTS
  Expressions of TLR2 and TLR4 in colonic epithelial cells on DSS-induced colitis were much higher than normal ones. After the treatment with TLR2mAb and TLR4mAb, DAI and HS were decreased significantly. The UC model group showed a conspicuous increase of Escherichia coli and decreases of Lactobacillus spp. and Bifidobacterium spp. After being treated with TLR2mAb or/and TLR4mAb, Lactobacillus spp. and Bifidobacterium spp. increased to the normal level.
  
  
  CONCLUSIONS
  TLR2mAb and TLR4mAb can suppress the development of DSS-induced colitis and increase counts of Lactobacilli and Bifidobacteria.
authors: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors: Le
authors: L
authors: Dong
authors: Juan
authors: J
authors: Li
authors: Yi
authors: Y
authors: Liu
authors: Wenjie
authors: W
authors: Yue
authors: Xiaoting
authors: X
authors: Luo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001644:Bifidobacterium / Q000187:drug effects* / Q000254:growth & development; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005243:Feces / Q000382:microbiology; D051550:I-kappa B Kinase / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D007778:Lactobacillus / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; C531463:Tab1 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015847:Interleukin-4; D007371:Interferon-gamma; D016264:Dextran Sulfate; D051550:I-kappa B Kinase; D048308:Mitogen-Activated Protein Kinase 14