2024-03-29T08:28:53Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/679762022-11-17T02:08:08Zhdl_2115_20040hdl_2115_121The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in ApcMin/+ miceOno, JunyaShime, HiroakiTakaki, HiromiTakashima, KenFunami, KenjiYoshida, SumitoTakeda, YoheiMatsumoto, MisakoKasahara, MasanoriSeya, TsukasaTLR3TICAM-1 (TRIF)c-MycIntestinal polyposis490Background: Intestinal tumorigenesis is promoted by myeloid differentiation primary response gene 88 (MyD88) activation in response to the components of microbiota in ApcMin/+ 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 ApcMin/+Ticam1-/- mice and their survival was compared to survival of ApcMin/+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 ApcMin/+ mice. TICAM-1 knockout resulted in shorter survival of mice compared to WT mice or mice with knockout of MyD88 in the ApcMin/+ background. Polyps were more frequently formed in the distal intestine of ApcMin/+Ticam1-/- mice than in ApcMin/+ mice. Infiltration of immune cells such as CD11b+ and CD8α+ cells into the polyps was detected histologically. CD11b and CD8α mRNAs were increased in polyps of ApcMin/+Ticam1-/- mice compared to ApcMin/+ mice. Gene expression of inducible nitric oxide synthase (iNOS), interferon (IFN)-γ, CXCL9 and IL-12p40 was increased in polyps of ApcMin/+Ticam1-/- mice. mRNA and protein expression of c-Myc, a critical transcription factor for inflammation-associated polyposis, were increased in polyps of ApcMin/+Ticam1-/- mice. A Lactobacillus strain producing dsRNA was detected in feces of ApcMin/+ mice. Conclusion: These results imply that the TLR3/TICAM-1 pathway inhibits polyposis through suppression of c-Myc expression and supports long survival in ApcMin/+ mice.BioMed CentralJournal Articleapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfapplication/pdfapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/2115/67976https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67976/2/12929_2017_387_MOESM1_ESM.docxhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67976/3/12929_2017_387_MOESM2_ESM.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67976/4/12929_2017_387_MOESM3_ESM.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67976/5/12929_2017_387_MOESM4_ESM.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67976/6/12929_2017_387_MOESM5_ESM.docxhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67976/1/s12929-017-0387-z.pdf1021-7770Journal of biomedical science24792017-10-17enginfo:doi/10.1186/s12929-017-0387-zhttp://creativecommons.org/licenses/by/4.0/publisher