{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:45:18Z","timestamp":1789731918068,"version":"4.0.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T00:00:00Z","timestamp":1431648000000},"content-version":"vor","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.0123498","type":"journal-article","created":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T17:59:39Z","timestamp":1431712779000},"page":"e0123498","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Intestinal Barrier in Irritable Bowel Syndrome: Subtype-Specific Effects of the Systemic Compartment in an In Vitro Model"],"prefix":"10.1371","volume":"10","author":[{"given":"Samefko","family":"Ludidi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Jonkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elhaseen","family":"Elamin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm-Jan","family":"Pieters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Schaepkens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bours","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kruimel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Conchillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad","family":"Masclee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,5,15]]},"reference":[{"issue":"5","key":"ref1","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1053\/j.gastro.2005.11.061","article-title":"Functional bowel disorders","volume":"130","author":"GF Longstreth","year":"2006","journal-title":"Gastroenterology"},{"issue":"6","key":"ref2","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1053\/gast.2002.37095","article-title":"AGA technical review on irritable bowel syndrome","volume":"123","author":"DA Drossman","year":"2002","journal-title":"Gastroenterology"},{"issue":"1 Suppl","key":"ref3","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1365-2982.2006.00875.x","article-title":"Mechanisms of hypersensitivity in IBS and functional disorders","volume":"19","author":"F Azpiroz","year":"2007","journal-title":"Neurogastroenterol Motil"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/ajg.2008.94","article-title":"Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms","volume":"104","author":"C Cremon","year":"2009","journal-title":"Am J Gastroenterol"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1053\/j.gastro.2003.11.055","article-title":"Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome","volume":"126","author":"G Barbara","year":"2004","journal-title":"Gastroenterology"},{"issue":"8","key":"ref6","doi-asserted-by":"crossref","first-page":"G529","DOI":"10.1152\/ajpgi.00207.2012","article-title":"The intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome","volume":"305","author":"Y Ringel","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"7","key":"ref7","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1053\/gast.2002.33579","article-title":"Activation of the mucosal immune system in irritable bowel syndrome","volume":"122","author":"VS Chadwick","year":"2002","journal-title":"Gastroenterology"},{"issue":"1","key":"ref8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/0016-5085(95)90267-8","article-title":"Altered rectal perception is a biological marker of patients with irritable bowel syndrome","volume":"109","author":"H Mertz","year":"1995","journal-title":"Gastroenterology"},{"key":"ref9","article-title":"The Confluence of Increased Permeability, Inflammation, and Pain in Irritable Bowel Syndrome","author":"M Camilleri","year":"2012","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"6","key":"ref10","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/j.1572-0241.2006.00667.x","article-title":"Mucosal barrier defects in irritable bowel syndrome. Who left the door open?","volume":"101","author":"G Barbara","year":"2006","journal-title":"Am J Gastroenterol"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1038\/ajg.2011.257","article-title":"The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype","volume":"106","author":"N Bertiaux-Vandaele","year":"2011","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"ref12","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1111\/j.1572-0241.2006.00672.x","article-title":"Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes","volume":"101","author":"SP Dunlop","year":"2006","journal-title":"Am J Gastroenterol"},{"issue":"1\u20132","key":"ref13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.pain.2009.06.017","article-title":"Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome","volume":"146","author":"Q Zhou","year":"2009","journal-title":"Pain"},{"issue":"11\u201312","key":"ref14","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1111\/j.1365-2036.2004.02284.x","article-title":"Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario","volume":"20","author":"JK Marshall","year":"2004","journal-title":"Aliment Pharmacol Ther"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1152\/physrev.00028.2003","article-title":"Protease-activated receptors: contribution to physiology and disease","volume":"84","author":"VS Ossovskaya","year":"2004","journal-title":"Physiol Rev"},{"issue":"8","key":"ref16","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/ajg.2013.152","article-title":"Luminal Cysteine-Proteases Degrade Colonic Tight Junction Structure and Are Responsible for Abdominal Pain in Constipation-Predominant IBS","volume":"108","author":"A Annahazi","year":"2013","journal-title":"Am J Gastroenterol"},{"issue":"5","key":"ref17","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1136\/gut.2007.140210","article-title":"Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity","volume":"57","author":"K Gecse","year":"2008","journal-title":"Gut"},{"issue":"5","key":"ref18","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.cgh.2006.12.004","article-title":"A pilot study of fecal serine-protease activity: a pathophysiologic factor in diarrhea-predominant irritable bowel syndrome","volume":"5","author":"R Roka","year":"2007","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"10","key":"ref19","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1007\/s10620-009-1094-8","article-title":"Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase","volume":"55","author":"JW Lee","year":"2010","journal-title":"Dig Dis Sci"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/00024382-199807000-00008","article-title":"Pure endotoxin does not pass across the intestinal epithelium in vitro","volume":"10","author":"R Benoit","year":"1998","journal-title":"Shock"},{"issue":"3","key":"ref21","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1086\/315784","article-title":"Localization of endotoxin in the rat intestinal epithelium","volume":"182","author":"Y Ge","year":"2000","journal-title":"J Infect Dis"},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"e35008","DOI":"10.1371\/journal.pone.0035008","article-title":"Effects of ethanol and acetaldehyde on tight junction integrity: in vitro study in a three dimensional intestinal epithelial cell culture model","volume":"7","author":"E Elamin","year":"2012","journal-title":"PLoS One"},{"issue":"3","key":"ref23","doi-asserted-by":"crossref","first-page":"e58561","DOI":"10.1371\/journal.pone.0058561","article-title":"Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model","volume":"8","author":"E Elamin","year":"2013","journal-title":"PLoS One"},{"issue":"1 Suppl","key":"ref24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2144\/000112517","article-title":"ImageJ for microscopy","volume":"43","author":"TJ Collins","year":"2007","journal-title":"Biotechniques"},{"issue":"4","key":"ref25","first-page":"413","article-title":"Effect of lipopolysaccharides on human dendritic cell cultures and its inhibition by polymyxin B","volume":"24","author":"A Cuellar","year":"2004","journal-title":"Biomedica"},{"issue":"6","key":"ref26","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1136\/gut.2009.181834","article-title":"MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome","volume":"59","author":"Q Zhou","year":"2010","journal-title":"Gut"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1136\/gut.47.6.804","article-title":"Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome","volume":"47","author":"RC Spiller","year":"2000","journal-title":"Gut"},{"issue":"11\u201312","key":"ref28","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/apt.12080","article-title":"Review article: Associations between immune activation, intestinal permeability and the irritable bowel syndrome","volume":"36","author":"J Matricon","year":"2012","journal-title":"Aliment Pharmacol Ther"},{"issue":"2","key":"ref29","doi-asserted-by":"crossref","first-page":"244","DOI":"10.5056\/jnm.2013.19.2.244","article-title":"Mucosal mast cell count is associated with intestinal permeability in patients with diarrhea predominant irritable bowel syndrome","volume":"19","author":"H Lee","year":"2013","journal-title":"J Neurogastroenterol Motil"},{"issue":"18","key":"ref30","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.1523\/JNEUROSCI.5679-03.2004","article-title":"Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia","volume":"24","author":"S Amadesi","year":"2004","journal-title":"J Neurosci"},{"issue":"Pt 3","key":"ref31","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1042\/bj3141009","article-title":"Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2","volume":"314","author":"SK Bohm","year":"1996","journal-title":"Biochem J"},{"issue":"4","key":"ref32","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1042\/BST0381072","article-title":"Developments in three-dimensional cell culture technology aimed at improving the accuracy of in vitro analyses","volume":"38","author":"DJ Maltman","year":"2010","journal-title":"Biochem Soc Trans"},{"issue":"8","key":"ref33","doi-asserted-by":"crossref","first-page":"e22967","DOI":"10.1371\/journal.pone.0022967","article-title":"Differential effects of TNF (TNFSF2) and IFN-gamma on intestinal epithelial cell morphogenesis and barrier function in three-dimensional culture","volume":"6","author":"K Juuti-Uusitalo","year":"2011","journal-title":"PLoS One"},{"key":"ref34","article-title":"Activation of the Epithelial-to-Mesenchymal Transition Factor Snail Mediates Acetaldehyde-Induced Intestinal Epithelial Barrier Disruption","author":"E Elamin","year":"2013","journal-title":"Alcohol Clin Exp Res"},{"issue":"8","key":"ref35","doi-asserted-by":"crossref","first-page":"G677","DOI":"10.1152\/ajpgi.00236.2013","article-title":"Ethanol disrupts intestinal epithelial tight junction integrity through intracellular calcium-mediated Rho\/ROCK activation","volume":"306","author":"E Elamin","year":"2014","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"7","key":"ref36","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1038\/ajg.2013.92","article-title":"Mast cell tryptase reduces junctional adhesion molecule-A (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome","volume":"108","author":"EM Wilcz-Villega","year":"2013","journal-title":"Am J Gastroenterol"},{"issue":"4","key":"ref37","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1081\/JAS-120002288","article-title":"Serum B12 tryptase level as a marker of allergic airway inflammation in asthma","volume":"39","author":"M Taira","year":"2002","journal-title":"J Asthma"},{"key":"ref38","article-title":"Paracellular permeability is increased by basal lipopolysaccharide in a primary culture of colonic epithelial cells; an effect prevented by an activator of Toll-like receptor-2","author":"PJ Hanson","year":"2007","journal-title":"Innate Immun"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ajpath.2012.10.014","article-title":"Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14","volume":"182","author":"S Guo","year":"2013","journal-title":"Am J Pathol"},{"issue":"3","key":"ref40","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/ibd.20019","article-title":"Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease","volume":"13","author":"O Pastor Rojo","year":"2007","journal-title":"Inflamm Bowel Dis"},{"issue":"12","key":"ref41","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1001\/archsurg.1988.01400360029003","article-title":"A single dose of endotoxin increases intestinal permeability in healthy humans","volume":"123","author":"ST O'Dwyer","year":"1988","journal-title":"Arch Surg"},{"issue":"10","key":"ref42","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1007\/s10620-012-2339-5","article-title":"Effects of proton pump inhibitor therapy in the distal gut: putting the pieces together","volume":"57","author":"D Keszthelyi","year":"2012","journal-title":"Dig Dis Sci"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/1471-230X-12-121","article-title":"Increased proton pump inhibitor and NSAID exposure in irritable bowel syndrome: results from a case-control study","volume":"12","author":"D Keszthelyi","year":"2012","journal-title":"BMC Gastroenterol"},{"issue":"2","key":"ref44","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1006\/excr.1998.4261","article-title":"Blockade of tumor cell transforming growth factor-betas enhances cell cycle progression and sensitizes human breast carcinoma cells to cytotoxic chemotherapy","volume":"245","author":"T Ohmori","year":"1998","journal-title":"Exp Cell Res"},{"issue":"5","key":"ref45","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.semcancer.2005.05.002","article-title":"Three-dimensional tissue culture models in cancer biology","volume":"15","author":"JB Kim","year":"2005","journal-title":"Semin Cancer Biol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0123498","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T02:25:14Z","timestamp":1540347914000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0123498"}},"subtitle":[],"editor":[{"given":"M\u00e1ria A.","family":"Deli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,5,15]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,5,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0123498","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,15]]}}}