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
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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