The Role of Cytokines in the Fibrotic Responses in Crohn's Disease.
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ABSTRACT:
SUBMITTER: Curciarello R
PROVIDER: S-EPMC5545939 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Crohn's disease (CD) is the main type of chronic inflammatory bowel disease of unknown etiology. Evidence from family and twin studies suggests that genetics plays a significant role in predisposing an individual to develop Crohn's disease. A susceptibility locus for Crohn's disease has been mapped 3 to chromosome 16: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators which is expressed in hematopoietic compartment cells and intestinal epithelial cells as well as in paneth cells, where NOD2 may play an important role in the pathogenesis of Crohn disease in the gastrointestinal system. This leads to alteration the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has two functions, first an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. Thus, NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in intestinal epithelial cells as well as in paneth cells. Further confirmation of a genetic predisposition comes from studies of the association between the human leukocyte antigen (HLA) system and CD. The immunogenetic predisposition may be considered an important requirement for the development of CD, as several alleles of human major histocompatibility complex had an association with CD. Although it is difficult to estimate the importance of this region in determining overall genetic susceptibility in a population, studies of HLA allele sharing within families suggest that this region contributes between 10% and 33% of the total genetic risk of Crohn's disease.
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