The pathogenesis of inflammatory bowel disease: translational implications for clinicians.
Research in the pathogenesis of inflammatory bowel disease (IBD) has dramatically broadened our understanding of these complex disorders. These clinical manifestations result from a dysregulated immune response in the presence of luminal bacteria. Recent identification of mutations in the NOD2 gene, a protein involved in the sensing of bacteria, offers genetic support for the model of perturbed host-microbial interactions in Crohn's disease. Several immunologic pathways have been identified that play a role in maintaining gut immune homeostasis. Abnormal expression of proinflammatory, deleterious cytokines such as tumor necrosis factor-a and interferon-g results in direct and indirect tissue damage. The search for specific causative microbial agents in IBD continues to be intense. This paper describes the advances in our understanding of IBD pathogenesis, with an emphasis on how this information is translated into patient care. The next stage of research will take advantage of such molecular biologic techniques to identify new pathogenetic mechanisms and targets for therapy tailored to individual patients.
Abreu
Maria T
MT
Department of Medicine, Division of Gastroenterology, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8631 West 3rd Street, Suite 245E, Los Angeles, CA 90048, USA. Maria.Abreu@cshs.org
D000818:Animals; D035843:Biomedical Research; D002352:Carrier Proteins / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D004751:Enteritis / Q000150:complications / Q000382:microbiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D007371:Interferon-gamma / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D002352:Carrier Proteins; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma