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- Title
Toll-like receptor 4 prevents AOM/DSS-induced colitis-associated colorectal cancer in Bacteroides fragilis gnotobiotic mice.
- Authors
Lee, Yen-Peng; Huang, Wen-Ching; Lin, Tien-Jen; Chiu, Chien-Chao; Wang, Yu-Chih; Chen, Yi-Hsun; Hung, Shao-Wen; Chuang, Hsiao-Li; Chen, Ter-Hsin
- Abstract
Bacteroides fragilis (BF) plays a critical role in developing and maintaining the mammalian immune system. We previously found that BF colonization could prevent inflammation and tumor formation in a germ-free (GF) colitis-associated colorectal cancer (CAC) mouse model. The role of Toll-like receptor 4 (TLR4) in CAC development has not been clearly elucidated in BF mono-colonized gnotobiotic mice. The wild-type (WT) and TLR4 knockout (T4K) germ-free mice were raised with or without BF colonization for 28 days (GF/WT, GF/T4K, BF/WT, and BF/T4K) and then CAC was induced under azoxymethane (AOM)/dextran sulfate sodium (DSS) administration. The results showed that tumor formation and tumor incidence were significantly inhibited in the BF/WT group compared to those observed in the GF/WT group. However, the tumor prevention effect was not observed in the BF/T4K group unlike in the BF/WT group. Moreover, the CAC histological severity of the BF/WT group was ameliorated, but more severe lesions were found in the GF/WT, GF/T4K, and BF/T4K groups. Immunohistochemistry showed decreased cell proliferation (PCNA, β-catenin) and inflammatory markers (iNOS) in the BF/WT group compared to those in the BF/T4K group. Taken together, BF mono-colonization of GF mice might prevent CAC via the TLR4 signal pathway.
- Subjects
COLORECTAL cancer; TOLL-like receptors; BACTEROIDES fragilis; INFLAMMATORY bowel diseases; MICE; SODIUM sulfate; CELL proliferation
- Publication
Human & Experimental Toxicology, 2021, Vol 40, Issue 4, p622
- ISSN
0960-3271
- Publication type
Article
- DOI
10.1177/0960327120954249