NOD2 (CARD 15) is a key molecular player in Crohn's Disease and plays a role in the cellular signaling pathways that control inflammatory responses.
Both NOD2 (CARD15) alleles are mutated in roughly 15% of patients with Crohn's disease, but functional effects are unclear.
| Muramyl dipeptide upregulates secretion of tumor necrosis factor-α induced by toll-like receptor ligands|
Dr van Heel and colleagues analyzed the cytokine response of peripheral blood mononuclear cells to muramyl dipeptide, the ligand for NOD2.
The investigative team found that muramyl dipeptide induced little tumor necrosis factor-α or interleukin 1β, but strong interleukin-8 secretion.
The team noted that muramyl dipeptide also substantially upregulated secretion of tumor necrosis factor-α and interleukin 1β induced by toll-like receptor ligands.
The investigators observed that these effects were abolished by the most common Crohn's NOD2 double mutant genotypes at low nanomolar muramyl dipeptide concentrations.
The researchers reported that the observed effects provide the basis to develop a test of NOD2 functional deficiency.
Dr van Heel's team concludes, “In Crohn's disease, there are defects in neutrophil recruitment driven by NOD2 and interleukin 8 and in cross talk between the NOD2 and toll-like receptor pathways."
"This suggests that the immune system fails to receive an early priming signal.”