PMID- 29041928
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20181113
IS  - 1423-0127 (Electronic)
IS  - 1021-7770 (Print)
IS  - 1021-7770 (Linking)
VI  - 24
IP  - 1
DP  - 2017 Oct 17
TI  - The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through 
      suppression of c-Myc in Apc (Min/+) mice.
PG  - 79
LID - 10.1186/s12929-017-0387-z [doi]
LID - 79
AB  - 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.
FAU - Ono, Junya
AU  - Ono J
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
AD  - Department of Microbiology Immunology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Shime, Hiroaki
AU  - Shime H
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
AD  - Department of Microbiology Immunology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Takaki, Hiromi
AU  - Takaki H
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
AD  - Department of Microbiology Immunology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Takashima, Ken
AU  - Takashima K
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
AD  - Department of Microbiology Immunology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Funami, Kenji
AU  - Funami K
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
AD  - Department of Microbiology Immunology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Yoshida, Sumito
AU  - Yoshida S
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
AD  - Department of Pathology I, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Takeda, Yohei
AU  - Takeda Y
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
FAU - Matsumoto, Misako
AU  - Matsumoto M
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
FAU - Kasahara, Masanori
AU  - Kasahara M
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
AD  - Department of Pathology I, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Seya, Tsukasa
AU  - Seya T
AD  - Department of Vaccine Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan. 
      seya-tu@pop.med.hokudai.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20171017
PL  - England
TA  - J Biomed Sci
JT  - Journal of biomedical science
JID - 9421567
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Myc protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (TLR3 protein, mouse)
RN  - 0 (Toll-Like Receptor 3)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/*genetics/metabolism
MH  - Animals
MH  - Colonic Polyps/*genetics
MH  - Colorectal Neoplasms/*genetics
MH  - Female
MH  - Intestinal Polyps/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins c-myc/*metabolism
MH  - *Signal Transduction
MH  - Toll-Like Receptor 3/*genetics/metabolism
PMC - PMC5646017
OTO - NOTNLM
OT  - Intestinal polyposis
OT  - TICAM-1 (TRIF)
OT  - TLR3
OT  - c-Myc
COIS- ETHICS APPROVAL: All animal research protocols for this work were reviewed and 
      approved by the Animal Safety Center, Hokkaido University, Japan. CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they 
      have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2017/10/19 06:00
MHDA- 2018/05/15 06:00
PMCR- 2017/10/17
CRDT- 2017/10/19 06:00
PHST- 2017/07/18 00:00 [received]
PHST- 2017/10/12 00:00 [accepted]
PHST- 2017/10/19 06:00 [entrez]
PHST- 2017/10/19 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2017/10/17 00:00 [pmc-release]
AID - 10.1186/s12929-017-0387-z [pii]
AID - 387 [pii]
AID - 10.1186/s12929-017-0387-z [doi]
PST - epublish
SO  - J Biomed Sci. 2017 Oct 17;24(1):79. doi: 10.1186/s12929-017-0387-z.