{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:35:41Z","timestamp":1790516141136,"version":"4.1.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2012,12,27]],"date-time":"2012-12-27T00:00:00Z","timestamp":1356566400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0052873","type":"journal-article","created":{"date-parts":[[2012,12,27]],"date-time":"2012-12-27T23:32:36Z","timestamp":1356651156000},"page":"e52873","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":46,"title":["PTGER4 Expression-Modulating Polymorphisms in the 5p13.1 Region Predispose to Crohn's Disease and Affect NF-\u03baB and XBP1 Binding Sites"],"prefix":"10.1371","volume":"7","author":[{"given":"J\u00fcrgen","family":"Glas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Seiderer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darina","family":"Czamara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pasciuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Diegelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wetzke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Olszak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"M\u00fcller-Myhsok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Balschun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Achkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Ilyas","family":"Kamboh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Duerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,12,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1056\/NEJMra020831","article-title":"Inflammatory bowel disease","volume":"347","author":"DK Podolsky","year":"2002","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"RJ Xavier","year":"2007","journal-title":"Nature"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/ncpgasthep0528","article-title":"Mechanisms of disease pathogenesis of Crohn's disease and ulcerative colitis","volume":"3","author":"RB Sartor","year":"2006","journal-title":"Nat Clin Pract Gastroenterol Hepatol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1053\/j.gastro.2007.08.032","article-title":"The genetics of inflammatory bowel disease","volume":"133","author":"JH Cho","year":"2007","journal-title":"Gastroenterology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease","volume":"411","author":"Y Ogura","year":"2001","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease","volume":"411","author":"JP Hugot","year":"2001","journal-title":"Nature"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1126\/science.1135245","article-title":"A genome-wide association study identifies IL23R as an inflammatory bowel disease gene","volume":"314","author":"RH Duerr","year":"2006","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"e819","DOI":"10.1371\/journal.pone.0000819","article-title":"rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1\/2 variants","volume":"2","author":"J Glas","year":"2007","journal-title":"PLoS ONE"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/ng1954","article-title":"A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1","volume":"39","author":"J Hampe","year":"2007","journal-title":"Nat Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/ng2032","article-title":"Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis","volume":"39","author":"JD Rioux","year":"2007","journal-title":"Nat Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1111\/j.1572-0241.2007.01694.x","article-title":"The ATG16L1 gene variants rs2241879 and rs2241880 (T300A) are strongly associated with susceptibility to Crohn's disease in the German population","volume":"103","author":"J Glas","year":"2007","journal-title":"Am J Gastroenterol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/ng2061","article-title":"Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility","volume":"39","author":"M Parkes","year":"2007","journal-title":"Nat Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1572-0241.2005.00361.x","article-title":"Increased expression of the chemokine fractalkine in Crohn's disease and association of the fractalkine receptor T280M polymorphism with a fibrostenosing disease phenotype","volume":"101","author":"S Brand","year":"2006","journal-title":"Am J Gastroenterol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1097\/01.MIB.0000168372.94907.d2","article-title":"The role of Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and CARD15\/NOD2 mutations in the susceptibility and phenotype of Crohn's disease","volume":"11","author":"S Brand","year":"2005","journal-title":"Inflamm Bowel Dis"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1084\/jem.20061401","article-title":"Interleukin-17 is a negative regulator of established allergic asthma","volume":"203","author":"S Schnyder-Candrian","year":"2006","journal-title":"J Exp Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1080\/00365520600703900","article-title":"Homozygosity for the CARD15 frameshift mutation 1007fs is predictive of early onset of Crohn's disease with ileal stenosis, entero-enteral fistulas, and frequent need for surgical intervention with high risk of re-stenosis","volume":"41","author":"J Seiderer","year":"2006","journal-title":"Scand J Gastroenterol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1097\/01.mib.0000235836.32176.5e","article-title":"Predictive value of the CARD15 variant 1007fs for the diagnosis of intestinal stenoses and the need for surgery in Crohn's disease in clinical practice: results of a prospective study","volume":"12","author":"J Seiderer","year":"2006","journal-title":"Inflamm Bowel Dis"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1111\/j.1365-2036.2006.03093.x","article-title":"The +1059G\/C polymorphism in the C-reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease","volume":"24","author":"D Thalmaier","year":"2006","journal-title":"Aliment Pharmacol Ther"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00251-005-0073-2","article-title":"Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease","volume":"58","author":"F Schnitzler","year":"2006","journal-title":"Immunogenetics"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e10373","DOI":"10.1371\/journal.pone.0010373","article-title":"Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset","volume":"5","author":"J Glas","year":"2010","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1371\/journal.pgen.0030058","article-title":"Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4","volume":"3","author":"C Libioulle","year":"2007","journal-title":"PLoS Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1172\/JCI0214459","article-title":"The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut","volume":"109","author":"K Kabashima","year":"2002","journal-title":"J Clin Invest"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1046\/j.1365-3083.2002.01096.x","article-title":"Expression of the EP4 prostaglandin E2 receptor subtype with rat dextran sodium sulphate colitis: colitis suppression by a selective agonist, ONO-AE1-329","volume":"56","author":"M Nitta","year":"2002","journal-title":"Scand J Immunol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1124\/jpet.106.111146","article-title":"The prevention of colitis by E Prostanoid receptor 4 agonist through enhancement of epithelium survival and regeneration","volume":"320","author":"GL Jiang","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"6003","DOI":"10.3748\/wjg.v11.i38.6003","article-title":"Haplotype of prostaglandin synthase 2\/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease","volume":"11","author":"DG Cox","year":"2005","journal-title":"World J Gastroenterol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"12647","DOI":"10.1074\/jbc.M312972200","article-title":"Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel disease. Evidence for involvement of the transcription factor Egr-1","volume":"279","author":"K Subbaramaiah","year":"2004","journal-title":"J Biol Chem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/sj.bjp.0705077","article-title":"The cyclopentenone prostaglandin 15-deoxy-delta(12,14)- PGJ2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat","volume":"138","author":"S Cuzzocrea","year":"2003","journal-title":"Br J Pharmacol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"e691","DOI":"10.1371\/journal.pone.0000691","article-title":"Systematic association mapping identifies NELL1 as a novel IBD disease gene","volume":"2","author":"A Franke","year":"2007","journal-title":"PLoS ONE"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/ng.549","article-title":"Genome-wide association identifies multiple ulcerative colitis susceptibility loci","volume":"42","author":"DP McGovern","year":"2010","journal-title":"Nat Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3109\/00365528909091339","article-title":"Classification of inflammatory bowel disease","volume":"Suppl 170","author":"JE Lennard-Jones","year":"1989","journal-title":"Scand J Gastroenterol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1155\/2005\/269076","article-title":"Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology","volume":"19 Suppl A","author":"MS Silverberg","year":"2005","journal-title":"Can J Gastroenterol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1136\/gut.2005.066340","article-title":"Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease","volume":"54","author":"HP T\u00f6r\u00f6k","year":"2005","journal-title":"Gut"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/nar\/26.1.362","article-title":"Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL","volume":"26","author":"T Heinemeyer","year":"1998","journal-title":"Nucleic Acids Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.cell.2008.07.021","article-title":"XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease","volume":"134","author":"A Kaser","year":"2008","journal-title":"Cell"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ng.717","article-title":"Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci","volume":"42","author":"A Franke","year":"2010","journal-title":"Nat Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ng.764","article-title":"Meta-analysis identifies 31 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 49","volume":"43","author":"CA Anderson","year":"2011","journal-title":"Nat Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease","volume":"491","author":"L Jostins","year":"2012","journal-title":"Nature"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1124\/jpet.111.190447","article-title":"Prevention of trinitrobenzene sulfonic acid-induced experimental colitis by oral administration of a poly(lactic-coglycolic acid microsphere containing prostaglandin E2 receptor subtype 4 agonist","volume":"341","author":"T Okamoto","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1124\/jpet.107.134510","article-title":"MF498 [N-{[4-(5,9-Diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide], a selective E prostanoid receptor 4 antagonist, relieves joint inflammation and pain in rodent models of rheumatoid and osteoarthritis","volume":"325","author":"P Clark","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1476-5381.2010.00647.x","article-title":"A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models","volume":"160","author":"Q Chen","year":"2010","journal-title":"Br J Pharmacol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nm.1968","article-title":"Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion","volume":"15","author":"C Yao","year":"2009","journal-title":"Nat Med"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.20082293","article-title":"Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2\/EP4 receptor signaling","volume":"206","author":"K Boniface","year":"2009","journal-title":"J Exp Med"},{"key":"ref43","first-page":"1152","article-title":"Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease","volume":"58","author":"S Brand","year":"2009","journal-title":"Gut 2009"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1365-2796.2008.01953.x","article-title":"NF-kappaB in inflammatory bowel disease","volume":"263","author":"I Atreya","year":"2008","journal-title":"J Intern Med"},{"key":"ref45","first-page":"473","article-title":"Prostaglandins and inflammation: the cyclooxygenase controversy","volume":"48","author":"O Morteau","year":"2000","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/sj.bjp.0706923","article-title":"Prostaglandin E2 receptor distribution and function in the gastrointestinal tract","volume":"149","author":"I Dey","year":"2006","journal-title":"Br J Pharmacol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"G967","DOI":"10.1152\/ajpgi.00532.2002","article-title":"PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum","volume":"285","author":"JL Gookin","year":"2003","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1172\/JCI6899","article-title":"Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2","volume":"105","author":"O Morteau","year":"2000","journal-title":"J Clin Invest"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.jaci.2006.04.036","article-title":"Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci","volume":"118","author":"T Kurz","year":"2006","journal-title":"J Allergy Clin Immunol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/01.fpc.0000239977.61841.fe","article-title":"Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma","volume":"17","author":"SH Kim","year":"2007","journal-title":"Pharmacogenet Genomics"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nm872","article-title":"Narumiya S. Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells","volume":"9","author":"K Kabashima","year":"2003","journal-title":"Nat Med"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1126\/science.1102901","article-title":"CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance","volume":"307","author":"JH Niess","year":"2005","journal-title":"Science"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.175","article-title":"Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease","volume":"40","author":"JC Barrett","year":"2008","journal-title":"Nat Genet"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/ng1345","article-title":"Genetic variation in DLG5 is associated with inflammatory bowel disease","volume":"36","author":"M Stoll","year":"2004","journal-title":"Nat Genet"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/ajg.2008.65","article-title":"rs224136 on chromosome 10q21.1 and variants in PHOX2B, NCF4, and FAM92B are not major genetic risk factors for susceptibility to Crohn's disease in the German population","volume":"104","author":"J Glas","year":"2009","journal-title":"Am J Gastroenterol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e14466","DOI":"10.1371\/journal.pone.0014466","article-title":"The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants","volume":"5","author":"J Glas","year":"2010","journal-title":"PLoS One"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s00535-010-0231-7","article-title":"The presence of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn's disease independent of the IL23R genotype","volume":"45","author":"M J\u00fcrgens","year":"2010","journal-title":"J Gastroenterol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0052873","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T10:22:29Z","timestamp":1589019749000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0052873"}},"subtitle":[],"editor":[{"given":"Yong-Gang","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,12,27]]},"references-count":57,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2012,12,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0052873","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,27]]}}}