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Bifidobacterium lactis inhibits NF-kappaB in intestinal epithelial cells and prevents acute colitis and colitis-associated colon cancer in mice

 Seung Won Kim  ;  Hee Man Kim  ;  Kyoung Min Yang  ;  Sun-Ah Kim  ;  Sung-Kyu Kim  ;  Min Ji An  ;  Jae Jun Park  ;  Sang Kil Lee  ;  Tae Il Kim  ;  Won Ho Kim  ;  Jae Hee Cheon 
 INFLAMMATORY BOWEL DISEASES, Vol.16(9) : 1514-1525, 2010 
Journal Title
Issue Date
Acute Disease ; Animals ; Azoxymethane/toxicity ; Bifidobacteriales Infections/prevention & control ; Bifidobacterium/physiology* ; Blotting, Western ; Carcinogens/toxicity ; Chronic Disease ; Colitis/chemically induced ; Colitis/complications ; Colitis/prevention & control* ; Colon/metabolism ; Colon/microbiology ; Colon/pathology ; Colonic Neoplasms/chemically induced ; Colonic Neoplasms/complications ; Colonic Neoplasms/prevention & control* ; Dextran Sulfate/toxicity ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells/metabolism ; Epithelial Cells/microbiology* ; Epithelial Cells/pathology ; Immunoenzyme Techniques ; Inflammation/chemically induced ; Inflammation/complications ; Inflammation/prevention & control ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology* ; Intestinal Mucosa/pathology ; Lipopolysaccharides/pharmacology ; Luciferases/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/antagonists & inhibitors* ; NF-kappa B/metabolism ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction
BACKGROUND: The aim of this study was to investigate the antiinflammatory effects of Bifidobacterium lactis on intestinal epithelial cells (IECs) and on experimental acute murine colitis and its tumor prevention effects on colitis-associated cancer (CAC) in mice.

METHODS: Human HT-29 cells were stimulated with IL-1beta, lipopolysaccharides, or tumor necrosis factor-alpha with and without B. lactis, and the effects of B. lactis on nuclear factor kappa B (NF-kappaB) signaling in IEC were examined. For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with and without B. lactis. Finally, we induced colonic tumors in mice by azoxymethane (AOM) and DSS and evaluated the effects of B. lactis on tumor growth.

RESULTS: B. lactis significantly suppressed NF-kappaB activation, including NF-kappaB-binding activity and NF-kappaB-dependent reporter gene expression in a dose-dependent manner, and suppressed IkappaB-alpha degradation, which correlated with the downregulation of NF-kappaB-dependent gene products. Moreover, B. lactis suppressed the development of acute colitis in mice. Compared with the DSS group, the severity of DSS-induced colitis as assessed by disease activity index, colon length, and histological score was reduced in the B. lactis-treated group. In the CAC model, the mean number and size of tumors in the B. lactis-treated group were significantly lower than those in the AOM group.

CONCLUSIONS: Our data demonstrate that B. lactis inhibits NF-kappaB and NF-kappaB-regulated genes in IEC and prevents acute colitis and CAC in mice. These results suggest that B. lactis could be a potential preventive agent for CAC as well as a therapeutic agent for inflammatory bowel disease.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Park, Jae Jun(박재준)
Lee, Sang Kil(이상길) ORCID logo https://orcid.org/0000-0002-0721-0364
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
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