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Review
. 2006 Mar 28;12(12):1829-41.
doi: 10.3748/wjg.v12.i12.1829.

Current concept on the pathogenesis of inflammatory bowel disease-crosstalk between genetic and microbial factors: pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take "toll" ?

Peter Laszlo Lakatos  1 , Simon Fischer, Laszlo Lakatos, Istvan Gal, Janos Papp
Affiliations
Review

Current concept on the pathogenesis of inflammatory bowel disease-crosstalk between genetic and microbial factors: pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take "toll" ?

Peter Laszlo Lakatos et al. World J Gastroenterol. .

Abstract

The pathogenesis of inflammatory bowel disease (IBD) is only partially understood. Various environmental and host (e.g. genetic-, epithelial-, immune and non-immune) factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Some genes are associated with IBD itself, while others increase the risk of ulcerative colitis (UC) or Crohn's disease (CD) or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBD. The article discusses the current information on the crosstalk between microbial and genetic factors (e.g. NOD2/CARD15, SLC22A46A5 and DLG5). The genetic data acquired in recent years help in understanding the pathogenesis of IBD and can identify a number of potential targets for therapeutic intervention. In the future, genetics may help more accurately diagnose and predict disease course in IBD.

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Figures

Figure 1
Figure 1
NOD2/TLR4 signaling pathway. NOD2 activation by CARD-CARD dimmer formation results in binding to RICK kinase (RIP-like interacting CLARP kinase). RICK then activates the nuclear factor kB inhibitor (IkB) kinase complex (IKK) via phosphorylation of IKKc. The IKK complex next phosphorylates IkB resulting in nuclear factor kB (NFkB) translocation to the nuclei and transcriptional activation of NFkB responsive genes, such as pro-inflammatory cytokines or defensins. TLR4 induces activation through other molecules (Myd88, IRAK and TRAF6).
Figure 2
Figure 2
Structure of NOD2/CARD15 protein and locations of the three main mutations.
Figure 3
Figure 3
Role of microbial factors and genetics in the pathogenesis of IBD.
See this image and copyright information in PMC

References

    1. Mayberry JF, Rhodes J. Epidemiological aspects of Crohn's disease: a review of the literature. Gut. 1984;25:886–899. - PMC - PubMed
    1. Farrokhyar F, Swarbrick ET, Irvine EJ. A critical review of epidemiological studies in inflammatory bowel disease. Scand J Gastroenterol. 2001;36:2–15. - PubMed
    1. Lakatos L, Mester G, Erdelyi Z, Balogh M, Szipocs I, Kamaras G, Lakatos PL. Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977-2001. World J Gastroenterol. 2004;10:404–409. - PMC - PubMed
    1. Lakatos L, Lakatos PL. [Etiopathogenesis of inflammatory bowel diseases] Orv Hetil. 2003;144:1853–1860. - PubMed
    1. Hugot JP. Inflammatory bowel disease: causes and consequences. Best Pract Res Clin Gastroenterol. 2004;18:447–449. - PubMed

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