{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:12:42Z","timestamp":1790802762432,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":2420,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"The Wellcome Trust","doi-asserted-by":"publisher","award":["078306"],"award-info":[{"award-number":["078306"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Broad Medical Research Program","award":["IBD-0197"],"award-info":[{"award-number":["IBD-0197"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["12\/IP\/1400"],"award-info":[{"award-number":["12\/IP\/1400"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC.<\/jats:p>","DOI":"10.1111\/cei.12617","type":"journal-article","created":{"date-parts":[[2015,5,6]],"date-time":"2015-05-06T05:37:49Z","timestamp":1430890669000},"page":"39-50","source":"Crossref","is-referenced-by-count":47,"title":["Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer: Diagnostic and therapeutic potential"],"prefix":"10.1093","volume":"181","author":[{"given":"B","family":"Flood","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Oficjalska","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Laukens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Fay","sequence":"additional","affiliation":[{"name":"Pathology Department, RCSI and Beaumont Hospital, Dublin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"O'Grady","sequence":"additional","affiliation":[{"name":"Pathology Department, RCSI and Beaumont Hospital, Dublin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Caiazza","sequence":"additional","affiliation":[{"name":"Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Sciences, University College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Heetun","sequence":"additional","affiliation":[{"name":"Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Sciences, University College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K H G","family":"Mills","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Sheahan","sequence":"additional","affiliation":[{"name":"Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Sciences, University College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E J","family":"Ryan","sequence":"additional","affiliation":[{"name":"Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Sciences, University College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G A","family":"Doherty","sequence":"additional","affiliation":[{"name":"Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Sciences, University College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Kay","sequence":"additional","affiliation":[{"name":"Pathology Department, RCSI and Beaumont Hospital, Dublin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E M","family":"Creagh","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,5,6]]},"reference":[{"key":"2021122010162366000_cei12617-bib-0001","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/ibd.21409","article-title":"IBD around the world: comparing the epidemiology, diagnosis, and treatment: proceedings of the World Digestive","volume":"17","author":"Baumgart","year":"2011","journal-title":"Inflamm Bowel Dis"},{"key":"2021122010162366000_cei12617-bib-0002","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1053\/j.gastro.2011.10.001","article-title":"Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review","volume":"142","author":"Molodecky","year":"2012","journal-title":"Gastroenterology"},{"key":"2021122010162366000_cei12617-bib-0003","doi-asserted-by":"crossref","first-page":"3839","DOI":"10.3748\/wjg.v18.i29.3839","article-title":"Colorectal cancer in inflammatory bowel disease: what is the real magnitude of the risk?","volume":"18","author":"Dyson","year":"2012","journal-title":"World J Gastroenterol"},{"key":"2021122010162366000_cei12617-bib-0004","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1136\/gut.48.4.526","article-title":"The risk of colorectal cancer in ulcerative colitis: a meta-analysis","volume":"48","author":"Eaden","year":"2001","journal-title":"Gut"},{"key":"2021122010162366000_cei12617-bib-0005","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.cgh.2013.06.023","article-title":"Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case\u2013control study","volume":"11","author":"Rubin","year":"2013","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2021122010162366000_cei12617-bib-0006","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3322\/caac.20107","article-title":"Global cancer statistics","volume":"61","author":"Jemal","year":"2011","journal-title":"CA Cancer J Clin"},{"key":"2021122010162366000_cei12617-bib-0007","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3748\/wjg.14.378","article-title":"Cancer in inflammatory bowel disease","volume":"14","author":"Xie","year":"2008","journal-title":"World J Gastroenterol"},{"key":"2021122010162366000_cei12617-bib-0008","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1053\/j.gastro.2010.01.058","article-title":"Inflammation and colon cancer","volume":"138","author":"Terzic","year":"2010","journal-title":"Gastroenterology"},{"key":"2021122010162366000_cei12617-bib-0009","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/sj.cdd.4400598","article-title":"Caspase structure, proteolytic substrates, and function during apoptotic cell death","volume":"6","author":"Nicholson","year":"1999","journal-title":"Cell Death Differ"},{"key":"2021122010162366000_cei12617-bib-0010","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.it.2014.10.004","article-title":"Caspase crosstalk: integration of apoptotic and innate immune signalling pathways","volume":"35","author":"Creagh","year":"2014","journal-title":"Trends Immunol"},{"key":"2021122010162366000_cei12617-bib-0011","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1136\/gut.30.6.835","article-title":"Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease","volume":"30","author":"Mahida","year":"1989","journal-title":"Gut"},{"key":"2021122010162366000_cei12617-bib-0012","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.4049\/jimmunol.162.11.6829","article-title":"IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells","volume":"162","author":"Pizarro","year":"1999","journal-title":"J Immunol"},{"key":"2021122010162366000_cei12617-bib-0013","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.ejca.2006.01.010","article-title":"Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour\u2013host interactions","volume":"42","author":"Apte","year":"2006","journal-title":"Eur J Cancer"},{"key":"2021122010162366000_cei12617-bib-0014","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1073\/pnas.97.2.734","article-title":"IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1","volume":"97","author":"Vidal-Vanaclocha","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021122010162366000_cei12617-bib-0015","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1053\/j.gastro.2012.11.035","article-title":"Complex roles of caspases in the pathogenesis of inflammatory bowel disease","volume":"144","author":"Becker","year":"2013","journal-title":"Gastroenterology"},{"key":"2021122010162366000_cei12617-bib-0016","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/sj.cdd.4402038","article-title":"Inflammatory caspases and inflammasomes: master switches of inflammation","volume":"14","author":"Martinon","year":"2007","journal-title":"Cell Death Differ"},{"key":"2021122010162366000_cei12617-bib-0017","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.4049\/jimmunol.1101620","article-title":"Caspase-4 is required for activation of inflammasomes","volume":"188","author":"Sollberger","year":"2012","journal-title":"J Immunol"},{"key":"2021122010162366000_cei12617-bib-0018","doi-asserted-by":"crossref","first-page":"335","DOI":"10.4049\/jimmunol.1303424","article-title":"A critical role for human caspase-4 in endotoxin sensitivity","volume":"193","author":"Kajiwara","year":"2014","journal-title":"J Immunol"},{"key":"2021122010162366000_cei12617-bib-0019","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol Cell"},{"key":"2021122010162366000_cei12617-bib-0020","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.humpath.2007.10.015","article-title":"Mutational analysis of caspase 1, 4, and 5 genes in common human cancers","volume":"39","author":"Soung","year":"2008","journal-title":"Hum Pathol"},{"key":"2021122010162366000_cei12617-bib-0021","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.humpath.2008.11.013","article-title":"Mutational analysis of CASP1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 14 genes in gastrointestinal stromal tumors","volume":"40","author":"Kim","year":"2009","journal-title":"Hum Pathol"},{"key":"2021122010162366000_cei12617-bib-0022","first-page":"2995","article-title":"Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype","volume":"59","author":"Schwartz","year":"1999","journal-title":"Cancer Res"},{"key":"2021122010162366000_cei12617-bib-0023","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nrc1299","article-title":"A census of human cancer genes","volume":"4","author":"Futreal","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"2021122010162366000_cei12617-bib-0024","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature10558","article-title":"Non-canonical inflammasome activation targets caspase-11","volume":"479","author":"Kayagaki","year":"2011","journal-title":"Nature"},{"key":"2021122010162366000_cei12617-bib-0025","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.cell.2012.07.007","article-title":"TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by Gram-negative bacteria","volume":"150","author":"Rathinam","year":"2012","journal-title":"Cell"},{"key":"2021122010162366000_cei12617-bib-0026","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0092-8674(00)80943-5","article-title":"Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE","volume":"92","author":"Wang","year":"1998","journal-title":"Cell"},{"key":"2021122010162366000_cei12617-bib-0027","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":"Barrett","year":"2008","journal-title":"Nat Genet"},{"key":"2021122010162366000_cei12617-bib-0028","doi-asserted-by":"crossref","first-page":"0034.1","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT\u2013PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol"},{"key":"2021122010162366000_cei12617-bib-0029","first-page":"2106","article-title":"Physicians\u2019 perceptions of dysplasia and approaches to surveillance colonoscopy in ulcerative colitis","volume":"90","author":"Bernstein","year":"1995","journal-title":"Am J Gastroenterol"},{"key":"2021122010162366000_cei12617-bib-0030","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1183\/09031936.00105013","article-title":"Elevated expression of the NLRP3 inflammasome in neutrophilic asthma","volume":"43","author":"Simpson","year":"2014","journal-title":"Eur Respir J"},{"key":"2021122010162366000_cei12617-bib-0031","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1177\/1753425913507096","article-title":"Cis-resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages","volume":"20","author":"Huang","year":"2013","journal-title":"Innate Immun"},{"key":"2021122010162366000_cei12617-bib-0032","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.4049\/jimmunol.1400501","article-title":"Protective role for caspase-11 during acute experimental murine colitis","volume":"194","author":"Oficjalska","year":"2015","journal-title":"J Immunol"},{"key":"2021122010162366000_cei12617-bib-0033","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1038\/mi.2014.36","article-title":"Caspase-11 is expressed in the colonic mucosa and protects against dextran sodium sulfate-induced colitis","volume":"7","author":"Demon","year":"2014","journal-title":"Mucosal Immunol"},{"key":"2021122010162366000_cei12617-bib-0034","doi-asserted-by":"crossref","first-page":"39920","DOI":"10.1074\/jbc.M007255200","article-title":"Expression analysis of the human caspase-1 subfamily reveals specific regulation of the CASP5 gene by lipopolysaccharide and interferon-gamma","volume":"275","author":"Lin","year":"2000","journal-title":"J Biol Chem"},{"key":"2021122010162366000_cei12617-bib-0035","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1158\/1541-7786.MCR-05-0261","article-title":"Inflammation, a key event in cancer development","volume":"4","author":"Lu","year":"2006","journal-title":"Mol Cancer Res"},{"key":"2021122010162366000_cei12617-bib-0036","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.0105-2896.2004.00199.x","article-title":"Cytokines in cancer immunity and immunotherapy","volume":"202","author":"Smyth","year":"2004","journal-title":"Immunol Rev"},{"key":"2021122010162366000_cei12617-bib-0037","doi-asserted-by":"crossref","first-page":"e66909","DOI":"10.1371\/journal.pone.0066909","article-title":"Identification of an effective early signaling signature during neo-vasculogenesis in vivo by ex vivo proteomic profiling","volume":"8","author":"Rohban","year":"2013","journal-title":"PLOS ONE"},{"key":"2021122010162366000_cei12617-bib-0038","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.3748\/wjg.v20.i15.4189","article-title":"Hallmarks in colorectal cancer: angiogenesis and cancer stem-like cells","volume":"20","author":"Mathonnet","year":"2014","journal-title":"World J Gastroenterol"},{"key":"2021122010162366000_cei12617-bib-0039","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2004.07.013","article-title":"IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer","volume":"118","author":"Greten","year":"2004","journal-title":"Cell"},{"key":"2021122010162366000_cei12617-bib-0040","doi-asserted-by":"crossref","first-page":"8480","DOI":"10.4049\/jimmunol.179.12.8480","article-title":"Caspase-4 interacts with TNF receptor-associated factor 6 and mediates lipopolysaccharide-induced NF-kappaB-dependent production of IL-8 and CC chemokine ligand 4 (macrophage-inflammatory protein-1)","volume":"179","author":"Lakshmanan","year":"2007","journal-title":"J Immunol"},{"key":"2021122010162366000_cei12617-bib-0041","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/ibd.20766","article-title":"Diagnosis and management of dysplasia in patients with ulcerative colitis and Crohn's disease of the colon","volume":"15","author":"Ullman","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"2021122010162366000_cei12617-bib-0042","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/0046-8177(89)90273-6","article-title":"Observer study of the grading of dysplasia in ulcerative colitis: comparison with clinical outcome","volume":"20","author":"Melville","year":"1989","journal-title":"Hum Pathol"},{"key":"2021122010162366000_cei12617-bib-0043","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1136\/gut.52.8.1127","article-title":"Ten year follow up of ulcerative colitis patients with and without low grade dysplasia","volume":"52","author":"Lim","year":"2003","journal-title":"Gut"},{"key":"2021122010162366000_cei12617-bib-0044","first-page":"339","article-title":"Colorectal cancer in idiopathic inflammatory bowel disease","volume":"13","author":"Harpaz","year":"1996","journal-title":"Semin Diagn Pathol"},{"key":"2021122010162366000_cei12617-bib-0045","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.gastro.2003.08.023","article-title":"Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis","volume":"125","author":"Ullman","year":"2003","journal-title":"Gastroenterology"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.12617","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cei.12617","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cei.12617","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/181\/1\/39\/41792022\/cei12617.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/181\/1\/39\/41792022\/cei12617.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T03:49:35Z","timestamp":1691639375000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/181\/1\/39\/6422155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,6]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,5,6]]},"published-print":{"date-parts":[[2015,6,5]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.12617","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,7]]},"published":{"date-parts":[[2015,5,6]]}}}