1. Toll-like receptor 4 prevents AOM/DSS-induced colitis-associated colorectal cancer in Bacteroides fragilis gnotobiotic mice.
- Author
-
Lee, Yen-Peng, Huang, Wen-Ching, Lin, Tien-Jen, Chiu, Chien-Chao, Wang, Yu-Chih, Chen, Yi-Hsun, Hung, Shao-Wen, Chuang, Hsiao-Li, and Chen, Ter-Hsin
- Subjects
COLORECTAL cancer ,TOLL-like receptors ,BACTEROIDES fragilis ,INFLAMMATORY bowel diseases ,MICE ,SODIUM sulfate ,CELL proliferation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF