| First Author | Ono J | Year | 2017 |
| Journal | J Biomed Sci | Volume | 24 |
| Issue | 1 | Pages | 79 |
| PubMed ID | 29041928 | Mgi Jnum | J:271935 |
| Mgi Id | MGI:6282326 | Doi | 10.1186/s12929-017-0387-z |
| Citation | Ono J, et al. (2017) The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in Apc (Min/+) mice. J Biomed Sci 24(1):79 |
| abstractText | BACKGROUND: Intestinal tumorigenesis is promoted by myeloid differentiation primary response gene 88 (MyD88) activation in response to the components of microbiota in Apc (Min/+) mice. Microbiota also contains double-stranded RNA (dsRNA), a ligand for TLR3, which activates the toll-like receptor adaptor molecule 1 (TICAM-1, also known as TRIF) pathway. METHODS: We established Apc (Min/+) Ticam1 (-/-) mice and their survival was compared to survival of Apc (Min/+) Myd88 (-/-) and wild-type (WT) mice. The properties of polyps were investigated using immunofluorescence staining and RT-PCR analysis. RESULTS: We demonstrate that TICAM-1 is essential for suppression of polyp formation in Apc (Min/+) mice. TICAM-1 knockout resulted in shorter survival of mice compared to WT mice or mice with knockout of MyD88 in the Apc (Min/+) background. Polyps were more frequently formed in the distal intestine of Apc (Min/+) Ticam1 (-/-) mice than in Apc (Min/+) mice. Infiltration of immune cells such as CD11b(+) and CD8alpha(+) cells into the polyps was detected histologically. CD11b and CD8alpha mRNAs were increased in polyps of Apc (Min/+) Ticam1 (-/-) mice compared to Apc (Min/+) mice. Gene expression of inducible nitric oxide synthase (iNOS), interferon (IFN)-gamma, CXCL9 and IL-12p40 was increased in polyps of Apc (Min/+) Ticam1 (-/-) mice. mRNA and protein expression of c-Myc, a critical transcription factor for inflammation-associated polyposis, were increased in polyps of Apc (Min/+) Ticam1 (-/-) mice. A Lactobacillus strain producing dsRNA was detected in feces of Apc (Min/+) mice. CONCLUSION: These results imply that the TLR3/TICAM-1 pathway inhibits polyposis through suppression of c-Myc expression and supports long survival in Apc (Min/+) mice. |
