Further insights into Crohn’s disease

Abstract

Although the exact cause of Crohn’s disease remains unknown, genetic and environmental factors that affect host-microbe interactions in the gut are thought to play major roles in its etiology. Mutations in the Nod2 gene, which helps the immune system recognize bacteria in the gut, are known to increase susceptibility to the disease. Two reports in February 4, 2005 Science have provided new insights into the normal physiological role of Nod proteins and how impaired Nod function leads to inflammation.In the first report, researchers headed by Dr. Michael Karin, professor of pharmacology at the University of California at San Diego School of Medicine in La Jolla, observed that Nod mutations in mice, equivalent to the Nod2 mutations found in patients with Crohn’s disease, made the animals more susceptible to bacterial-induced intestinal inflammation. The mice also showed elevated levels of 2 key signaling molecules involved in inflammation, nuclear factor κ-B (NF-κB), and cytokine interleukin-1β (IL-1β). “Mutant mice exhibited elevated NF-κB activation in response to MDP (bacteria-derived muramyl dipeptide) and more efficient processing and secretion of the cytokine interleukin-1β (IL-1β). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-κB activation and IL-1β secretion,” the authors state.Writing also in this issue of Science, researchers led by Dr. Richard Flavell, professor and chairman of immunobiology, and professor of molecular, cellular, & developmental biology at Yale University School of Medicine, found that Nod2-deficient mice were susceptible to oral bacterial infections and that this vulnerability corresponded with impaired responses by Nod2-deficient cells to molecules that bind to Nod2. These mice also had lower concentrations of anti-microbial peptides in their gut, which the authors suggest indicates that a similar defect may contribute to inflammatory bowel disease in humans.More details can be found in Science, February 4, 2005 Although the exact cause of Crohn’s disease remains unknown, genetic and environmental factors that affect host-microbe interactions in the gut are thought to play major roles in its etiology. Mutations in the Nod2 gene, which helps the immune system recognize bacteria in the gut, are known to increase susceptibility to the disease. Two reports in February 4, 2005 Science have provided new insights into the normal physiological role of Nod proteins and how impaired Nod function leads to inflammation. In the first report, researchers headed by Dr. Michael Karin, professor of pharmacology at the University of California at San Diego School of Medicine in La Jolla, observed that Nod mutations in mice, equivalent to the Nod2 mutations found in patients with Crohn’s disease, made the animals more susceptible to bacterial-induced intestinal inflammation. The mice also showed elevated levels of 2 key signaling molecules involved in inflammation, nuclear factor κ-B (NF-κB), and cytokine interleukin-1β (IL-1β). “Mutant mice exhibited elevated NF-κB activation in response to MDP (bacteria-derived muramyl dipeptide) and more efficient processing and secretion of the cytokine interleukin-1β (IL-1β). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-κB activation and IL-1β secretion,” the authors state. Writing also in this issue of Science, researchers led by Dr. Richard Flavell, professor and chairman of immunobiology, and professor of molecular, cellular, & developmental biology at Yale University School of Medicine, found that Nod2-deficient mice were susceptible to oral bacterial infections and that this vulnerability corresponded with impaired responses by Nod2-deficient cells to molecules that bind to Nod2. These mice also had lower concentrations of anti-microbial peptides in their gut, which the authors suggest indicates that a similar defect may contribute to inflammatory bowel disease in humans. More details can be found in Science, February 4, 2005