Open Access

REVIEW

NOD2 engagement induces proinflammatory cytokine production, but not apoptosis, in leukocytes isolated from patients with Crohn’s disease

Evelien Bodar^1,3, Mihai G. Netea^1,3, Dirk J. de Jong², Bart-Jan Kullberg^1,3, Leo A. B. Joosten^1,3, Jos W. M. Van der Meer^1,3

1 Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
2 Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
3 Nijmegen University Center for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands

* Corresponding Author: J. W.M. van der Meer,

European Cytokine Network 2008, 19(4), 185-189. https://doi.org/10.1684/ecn.2008.0140

Accepted 19 November 2008;

Abstract

Background. NOD2/CARD15 is a member of the NACHT-LRR (NLR) family of proteins, which recognize the muramyl dipeptide motif from bacterial peptidoglycans. NOD2 has been shown to be involved in the pathogenesis of Crohn’s disease. NLR proteins modulate inflammation and apoptosis, and several studies have implicated NOD2 in the induction of cytokines and inflammatory reactions. However, only scarce data are available regarding its role in apoptosis. Donors and methods. Neutrophils and lymphocytes isolated from the blood from four Crohn’s disease patients homozygous for the loss-of-function 3020insC NOD2 mutation were examined for spontaneous and anisomycin-induced apoptosis. They were compared with cells from healthy con-trols and Crohn’s disease patients bearing the wild-type NOD2 allele. Cytokine production after stimulation of mononuclear cells (MNCs) with muramyl dipeptide was assessed by specific immunoassays. Results. We observed that MNCs isolated from the blood of patients with Crohn’s disease bearing the loss of function muta-tion in NOD2 displayed defective muramyl dipeptide-induced cytokine responses, but both granulocytes and lymphocytes from the same donors displayed normal apoptosis. Conclusions. NOD2 engagement by MDP mainly triggers cytokine activation and inflammatory reactions, but has negligible effects on cell apoptosis.

---

Keywords

---