NOD2: a potential target for regulating liver injury

被引：34

作者：

Body-Malapel, Mathilde ^{[1
,2
]}

Dharancy, Sebastien ^{[1
,2
]}

Berrebi, Dominique ^{[4
]}

Louvet, Alexandre ^{[1
,2
]}

Hugot, Jean-Pierre ^{[5
]}

Philpott, Dana J. ^{[6
]}

Giovannini, Marco ^{[7
]}

Chareyre, Fabrice ^{[7
]}

Pages, Gilles ^{[8
]}

Gantier, Emilie ^{[2
]}

Girardin, Stephen E. ^{[9
]}

Garcia, Irene ^{[10
]}

Hudault, Sylvie ^{[11
]}

Conti, Filomena ^{[12
]}

Sansonetti, Philippe J. ^{[13
]}

Chamaillard, Mathias ^{[1
,2
,3
]}

Desreumaux, Pierre ^{[1
,2
,3
]}

Dubuquoy, Laurent ^{[1
,2
,3
]}

Mathurin, Philippe ^{[1
,2
,3
]}

机构：

[1] CHU Lille, Hop Huriez, Serv Appareil Digestif Nutr, F-59037 Lille, France

[2] INSERM, U795, Lille, France

[3] Univ Lille 2, F-59800 Lille, France

[4] Univ Paris 07, Hop Robert Debre, Serv Anat & Cytol Pathol, APHP,France & Equipe Accueli 3102, Paris, France

[5] Hop Robert Debre, INSERM, U843, Paris, France

[6] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[7] Fdn Jean Dausset CEPH, INSERM, Genom Fonctionnelle Tumeurs Solides, Paris, France

[8] Univ Sophia Antipolis, Fac Sci, CNRS, Unite Mixte Rech 6543, Nice, France

[9] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[10] Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland

[11] Univ Paris 11, Fac Pharm, INSERM, U510, Chatenay Malabry, France

[12] Univ Paris 05, Hop Cochin, Serv Chirurg, Lab Biol Cellulaire, Paris, France

[13] INSERM, Inst Pasteur, U786, Paris, France

来源：

LABORATORY INVESTIGATION | 2008年 / 88卷 / 03期

关键词：

inflammation; innate immunity; liver; NOD2; lymphocyte;

D O I：

10.1038/labinvest.3700716

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The recent discovery of bacterial receptors such as NOD2 that contribute to crosstalk between innate and adaptive immune systems in the digestive tract constitutes an important challenge in our understanding of liver injury mechanisms. The present study focuses on NOD2 functions during liver injury. NOD2, TNF-alpha and IFN-gamma mRNA were quantified using real-time PCR in liver samples from patients and mice with liver injury. We evaluated the susceptibility of concanavalin A (ConA) challenge in NOD2-deficient mice (Nod2(-/-)) compared to wild-type littermates. We tested the effect of muramyl dipeptide (MDP), the specific activator of NOD2, on ConA-induced liver injury in C57BL/6 mice. We studied the cellular distribution and the role of NOD2 in immune cells and hepatocytes. We demonstrated that NOD2, TNF-a and IFN-gamma were upregulated during liver injury in mice and humans. Nod2(-\-) mice were resistant to ConA-induced hepatitis compared to their wild-type littermates, through reduced IFN-gamma production by immune cells. Conversely, administration of MDP exacerbated ConA-induced liver injury. MDP was a strong inducer of IFN-gamma in freshly isolated human PBMC, splenocytes and hepatocytes. Our study supports the hypothesis that NOD2 contributes to liver injury via a regulatory mechanism affecting immune cells infiltrating the liver and hepatocytes. Taken together, our results indicate that NOD2 may represent a new therapeutic target in liver diseases.

引用

页码：318 / 327

页数：10

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