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01-04-2016 | Original Article—Alimentary Tract

N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis

Authors: Shinichiro Shinzaki, Mayuko Ishii, Hironobu Fujii, Hideki Iijima, Kana Wakamatsu, Shoichiro Kawai, Eri Shiraishi, Satoshi Hiyama, Takahiro Inoue, Yoshito Hayashi, Ryusuke Kuwahara, Shinji Takamatsu, Yoshihiro Kamada, Eiichi Morii, Masahiko Tsujii, Tetsuo Takehara, Eiji Miyoshi

Published in: Journal of Gastroenterology | Issue 4/2016

Abstract

Background

Oligosaccharide structures and their alterations have important roles in modulating intestinal inflammation. N-Acetylglucosaminyltransferase V (GnT-V) is involved in the biosynthesis of N-acetylglucosamine (GlcNAc) by β1,6-branching on N-glycans and is induced in various pathologic processes, such as inflammation and regeneration. GnT-V alters host immune responses by inhibiting the functions of CD4⁺ T cells and macrophages. The present study aimed to clarify the role of GnT-V in intestinal inflammation using GnT-V transgenic mice.

Methods

Colitis severity was compared between GnT-V transgenic mice and wild-type mice. β1,6-GlcNAc levels were investigated by phytohemagglutinin-L₄ lectin blotting and flow cytometry. We investigated phagocytosis of macrophages by measuring the number of peritoneal-macrophage-ingested fluorescent latex beads by flow cytometry. Cytokine production in the culture supernatant of mononuclear cells from the spleen, mesenteric lymph nodes, and bone-marrow-derived macrophages was determined by enzyme-linked immunosorbent assay. Clodronate liposomes were intravenously injected to deplete macrophages in vivo. Chronic-colitis-associated tumorigenesis was assessed after 9 months of repeated administration of dextran sodium sulfate (DSS).

Results

DSS-induced colitis and colitis induced by trinitrobenzene sulfonic acid were markedly exacerbated in GnT-V transgenic mice compared with wild-type mice. Production of interleukin-10 and phagocytosis of macrophages were significantly impaired in GnT-V transgenic mice compared with wild-type mice. Clodronate liposome treatment to deplete macrophages blocked the exacerbation of DSS-induced colitis and impairment of interleukin-10 production in GnT-V transgenic mice. Chronic-colitis-associated tumorigenesis was significantly increased in GnT-V transgenic mice.

Conclusions

Overexpression of GnT-V exacerbated murine experimental colitis by inducing macrophage dysfunction, thereby enhancing colorectal tumorigenesis.

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Title: N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis
Authors: Shinichiro Shinzaki
Mayuko Ishii
Hironobu Fujii
Hideki Iijima
Kana Wakamatsu
Shoichiro Kawai
Eri Shiraishi
Satoshi Hiyama
Takahiro Inoue
Yoshito Hayashi
Ryusuke Kuwahara
Shinji Takamatsu
Yoshihiro Kamada
Eiichi Morii
Masahiko Tsujii
Tetsuo Takehara
Eiji Miyoshi
Publication date: 01-04-2016
Publisher: Springer Japan
Published in: Journal of Gastroenterology / Issue 4/2016
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-015-1119-3

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N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis

Abstract

Background

Methods

Results

Conclusions

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