The Genetics of Inflammatory Bowel Disease

Limbergen, Johan Van; Russell, Richard K.; Nimmo, Elaine R.; Satsangi, Jack

doi:10.1111/j.1572-0241.2007.01527.x

Cited by 78 publications

(51 citation statements)

References 114 publications

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“…The pathophysiology of IBD is characterized by a highly activated state of the mucosal immune system and excessive mucosal damage (2). In recent years, important progress has been made in identifying and characterizing susceptibility genes for IBD (3). The (putative) functions of the proteins they encode corroborate the notion that the primary cause for the development of IBD originates from a dysregulated immune response to commensal intestinal bacteria, defects in mucosal barrier function, and/or bacterial clearance.…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 86%

Up-regulation and Cytoprotective Role of Epithelial Multidrug Resistance-associated Protein 1 in Inflammatory Bowel Disease

Blokzijl

Steenpaal

Borght

et al. 2008

Journal of Biological Chemistry

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MRP1 (multidrug resistance-associated protein 1) is well known for its role in providing multidrug resistance to cancer cells. In addition, MRP1 has been associated with both pro-and anti-inflammatory functions in nonmalignant cells. The pro-inflammatory function is evident from the fact that MRP1 is a high affinity transporter for cysteinyl-leukotriene C 4 (LTC 4 ), a lipid mediator of inflammation. It remains unexplained, however, why the absence of Mrp1 leads to increased intestinal epithelial damage in mice treated with dextran-sodium sulfate, a model for inflammatory bowel disease (IBD). We found that MRP1 expression is induced in the inflamed intestine of IBD patients, e.g. Crohn disease and ulcerative colitis. Increased MRP1 expression was detected at the basolateral membrane of intestinal epithelial cells. To study a putative role for MRP1 in protecting epithelial cells against inflammatory cues, we manipulated MRP1 levels in human epithelial DLD-1 cells and exposed these cells to cytokines and anti-Fas. Inhibition of MRP1 (by MK571 or RNA interference) resulted in increased cytokine-and antiFas-induced apoptosis of DLD-1 cells. Opposite effects, e.g. protection of DLD-1 cells against cytokine-and anti-Fas-induced apoptosis, were observed after recombinant MRP1 overexpression. Inhibition of LTC 4 synthesis reduced anti-Fas-induced apoptosis when MRP1 function was blocked, suggesting that LTC 4 is the pro-apoptotic compound exported by epithelial MRP1 during inflammation. These data show that MRP1 protects intestinal epithelial cells against inflammation-induced apoptotic cell death and provides a functional role for MRP1 in the inflamed intestinal epithelium of IBD patients.

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Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 86%

Up-regulation and Cytoprotective Role of Epithelial Multidrug Resistance-associated Protein 1 in Inflammatory Bowel Disease

Blokzijl

Steenpaal

Borght

et al. 2008

Journal of Biological Chemistry

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“…It is widely accepted that both diseases result from an inappropriate response of a defective mucosal immune system to indigenous flora and other luminal agents in a genetically susceptible host [2] . Eleven IBD genome-wide linkage analyses in families with multiple IBD affected members, as well as two different meta-analyses [3,4] have identified several linkage regions [5] . Following the identification of NOD2 (or CARD15), the first gene contributing to CD susceptibility (IBD1 locus), further fine mapping studies have identified a risk haplotype (IBD5 locus) on chromosome 5q [6] , along with two polymorphisms in the solute carrier family 22A4/22A5 (SLC22A4/A5) coding for OCTN1 and OCTN2, suggested as candidate genes [7] , and another polymorphism on the disk large homolog 5 (DLG5) gene [8] .…”

Section: Introductionmentioning

confidence: 99%

Replication of interleukin 23 receptor and autophagyrelated 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

Latiano¹,

Palmieri²,

Valvano³

et al. 2008

WJG

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RESULTS:The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced significantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult-and pediatric-onset subsets in our study population.

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“…Važna karika u nastanku upalnih procesa u probavnom sustavu jest genetska predispozicija (18), a vjeruje se da su CB i UK heterogene poligenske bolesti koje dijele neka područja genske podložnosti (19). Najvjerojatnije je fenotip UBC-a određen s nekoliko faktora, uključujući i interakciju među alelima, kao i utjecaj ostalih gena i čimbenika okoliša.…”

Section: Genetska Predispozicijaunclassified

Dipeptidyl Peptidase IV in Inflammatory Bowel Diseases (DPP IV/CD26)

Pučar

Detel

Varljen

2012

Archives of Industrial Hygiene and Toxicology

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Dipeptidil-peptidaza IV (DPP IV/CD26) i upalne bolesti crijevaUpalne bolesti crijeva (Crohnova bolest, ulcerozni kolitis, nedeterminirani kolitis) skupina su kroničnih autoimunosnih upalnih bolesti obilježenih ponavljanim upalama različitih dijelova gastrointestinalnog trakta koje su važan javnozdravstveni problem današnjice. Unatoč brojnim temeljnim i kliničkim istraživanjima etiologija ovih bolesti, kao i sama patogeneza upale ostaju nedovoljno razjašnjene. Dosadašnja su istraživanja potvrdila uzročno-posljedičnu vezu između medijatora upalnog odgovora i molekula uključenih u regulaciju njihove biološke aktivnosti, osobito proteaza. Cilj ovoga preglednog rada jest sažeti prikaz dosadašnjih saznanja o različitim aspektima upalnih bolesti crijeva, s posebnim naglaskom na potencijalnu ulogu i uključenost dipeptidil-peptidaze IV, odnosno molekule CD26 (DPP IV/CD26) u mehanizme nastanka upalnih procesa u probavnom sustavu. Dan je i pregled životinjskih modela kolitisa koji su znatno pridonijeli razumijevanju i terapiji ovih bolesti, s osobitim naglaskom na mišji model ulceroznog kolitisa (DSS-kolitis) te Crohnove bolesti (TNBS-kolitis).

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The Genetics of Inflammatory Bowel Disease

Cited by 78 publications

References 114 publications

Up-regulation and Cytoprotective Role of Epithelial Multidrug Resistance-associated Protein 1 in Inflammatory Bowel Disease

Up-regulation and Cytoprotective Role of Epithelial Multidrug Resistance-associated Protein 1 in Inflammatory Bowel Disease

Replication of interleukin 23 receptor and autophagyrelated 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

Dipeptidyl Peptidase IV in Inflammatory Bowel Diseases (DPP IV/CD26)

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