NEW YORK (Reuters Health) - The NOD2 gene is a known susceptibility locus for Crohn’s disease. Now, Dutch researchers have identified the mechanisms by which mutations in NOD2 mediate patients’ inflammatory responses.
In the July issue of the European Journal of Immunology, a multicenter team led by Dr. Mihai G. Netea of the University Medical Center St. Radboud in Nijmegen, report the results of genetic analyses performed on blood samples from 74 patients with Crohn’s disease and 10 healthy volunteers.
The investigators determined that patients with Crohn’s disease who carry the 3020insC frameshift mutation in the NOD2 gene have defective release of interleukin-10 from blood mononuclear cells in response to stimulation with Toll-like receptor 2 ligands but not in response to bacterial lipopolysaccharide, a Toll-like receptor 4 ligand.
Furthermore, the researchers found that when cells from patients with the NOD2 mutation were stimulated with Bacteroides fragilis, an organism known to play a role in the pathogenesis of Crohn’s disease, the ratio of IL-10 to transforming growth factor-beta “was significantly lower than in patients with the wild-type NOD2 allele and healthy volunteers.”
“In conclusion,” the authors write, “defective NOD2 function results in a pro-inflammatory cytokine bias after stimulation of mononuclear cells with Toll-like receptor 2 stimuli, and this could contribute to the overwhelming inflammation seen in Crohn’s disease.”
Source: Eur J Immunol 2004;34:2052-2059. [ Google search on this article ]
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