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The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in Apc Min/+ mice
- Source :
- Journal of Biomedical Science, Vol 24, Iss 1, Pp 1-9 (2017), Journal of Biomedical Science
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- 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. 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. 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 CD8α+ cells into the polyps was detected histologically. CD11b and CD8α 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)-γ, 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. 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.
- Subjects :
- Male
0301 basic medicine
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Colonic Polyps
lcsh:Medicine
Proto-Oncogene Proteins c-myc
Mice
03 medical and health sciences
Interferon
Intestinal polyposis
Gene expression
medicine
Animals
Pharmacology (medical)
TLR3
Receptor
Molecular Biology
Mice, Knockout
Messenger RNA
biology
Research
lcsh:R
Biochemistry (medical)
Intestinal Polyps
Cell Biology
General Medicine
Molecular biology
Toll-Like Receptor 3
Mice, Inbred C57BL
Nitric oxide synthase
Adaptor Proteins, Vesicular Transport
c-Myc
030104 developmental biology
Integrin alpha M
Immunology
biology.protein
CXCL9
Female
Colorectal Neoplasms
TICAM-1 (TRIF)
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 14230127
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of Biomedical Science
- Accession number :
- edsair.doi.dedup.....05180d43a2e943c3346898140bd7e98c