Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer: Diagnostic and therapeutic potential
Autor: | Debby Laukens, Elaine W. Kay, Emma M. Creagh, Zaid Heetun, Brian Flood, Kieran Sheahan, Khg Mills, Joanna Fay, Francesco Caiazza, Elizabeth J. Ryan, Glen A. Doherty, Anthony O'Grady, Katarzyna Oficjalska |
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Rok vydání: | 2015 |
Předmět: |
Male
Colorectal cancer Cellular homeostasis LIPOPOLYSACCHARIDE Inflammatory bowel disease NLRP3 INFLAMMASOME ACTIVATION 0302 clinical medicine Intestinal mucosa Immunology and Allergy Medicine MUTATIONAL ANALYSIS Intestinal Mucosa Caspase 0303 health sciences MUCOSA biology Translational Proteolytic enzymes Middle Aged Ulcerative colitis Caspases Initiator CROHNS-DISEASE 3. Good health caspases ULCERATIVE-COLITIS 030220 oncology & carcinogenesis Female medicine.symptom Colorectal Neoplasms Adult GENES Immunology colorectal cancer LOW-GRADE DYSPLASIA Inflammation Young Adult 03 medical and health sciences inflammatory bowel disease Humans Aged 030304 developmental biology business.industry Biology and Life Sciences Epithelial Cells medicine.disease digestive system diseases inflammation CELLS biology.protein Colitis Ulcerative business Biomarkers |
Zdroj: | CLINICAL AND EXPERIMENTAL IMMUNOLOGY Clinical and Experimental Immunology |
ISSN: | 1365-2249 0009-9104 |
Popis: | Summary 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. |
Databáze: | OpenAIRE |
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