N-acetylglucosaminyltransferase V exacerbates concanavalin A-induced hepatitis in mice.
Mol Med Rep
; 11(5): 3573-84, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25572342
ABSTRACT
NAcetylglucosaminyltransferase V (GnTV) catalyzes ß16 branching in asparaginelinked oligosaccharides and is one of the most important glycosyltransferases involved in carcinogenesis, cancer metastasis and immunity. To investigate the biological functions of GnTV, the present study developed GnTV transgenic (Tg) mice and the role of GnTV in experimental immunemediated hepatitis, induced by concanavalin A (ConA), were investigated. It was found that the aberrant expression of GnTV exacerbated ConAinduced hepatitis in the Tg mice compared with the wildtype (WT) mice. The survival rate of the ConAinduced hepatitis at a highdose of ConA was significantly lower in the Tg mice. Intravenously injected ConA is known to initially bind predominantly to the mannose gland of the liver sinusoidal endothelial cell (LSEC) surface and to leads to the activation of various immune cells. In the present study, the binding affinity of ConA to the LSECs did not differ between the WT and Tg mice. In addition, T cell receptor stimulation by anticluster of differentiation (CD)3/CD28 antibodies produced lower levels of T helper (Th)1 cytokine (interferonγ) and higher levels of Th2 cytokine (interleukin10) in the Tg mouse splenic lymphocytes compared with WT mice. The composition of the hepatic mononuclear cells revealed that CD11bpositive cells were significantly increased in the GnTV Tg mice. In addition, F4/80positive cells were significantly increased in the Tg mouse liver and the depletion of macrophages reduced the difference in the severity of ConAinduced hepatitis between the WT and Tg mice. In conclusion, the present findings indicated that the aberrant expression of GnTV led to an increase in hepatic macrophage infiltration and enhanced ConAinduced hepatitis. Modulation of glycosylation may be a novel therapeutic target for immunityassociated acute hepatitis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
N-Acetilglucosaminiltransferasas
/
Enfermedad Hepática Inducida por Sustancias y Drogas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón