It can recognize and respond to a component found in the cell wall of bacteria, muramyl dipeptide (MDP), and has been shown to play an important role in the innate immune response of macrophages to bacterial infections. However, the function of NOD2 in the gastrointestinal tract and the colon and its contribution of mutant NOD2 alleles to the pathogenesis of CD is still unclear.
A research article to be published on October 14, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Professor Simon Carding from the University of Leeds used in vivo and in vitro studies to analyse the specific function of NOD2 in colonic epithelial cells.
They found that NOD2 was predominantly expressed in epithelial cells at the base of colonic crypts, where the majority of cells are undergoing proliferation. In addition, NOD2's ligand, MDP, stimulated the growth of in vitro cultures of colonic epithelial cells. Further evidence for the role of NOD2 in cell growth and survival was obtained using NOD2-deficient mice and RNA interference. In the absence of NOD2 colonic epithelial cells proliferation was reduced and apoptosis increased, which were exacerbated when challenged with the enteric pathogen, Salmonella typhimurium. Surprisingly the ability of NOD2 to promote cell growth and survival was also apparent in the colorectal cancer cells as the introduction of siRNAs specific for NOD2 resulted in an 80% decrease in survival compared to cells treated with control NOD2 siRNA.
These results highlight for the first time the importance of NOD2 in the regulation of epithelial cell growth and survival and consequently the integrity of the intestinal epithelial cell barrier, that is required for protection against pathogenic and opportunistic bacterial infections. further investigation is needed to assess if these receptors work alongside each other in the regulation of epithelial cell homeostasis.
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