TY - JOUR
T1 - Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer
T2 - Diagnostic and therapeutic potential
AU - Flood, B.
AU - Oficjalska, K.
AU - Laukens, D.
AU - Fay, J.
AU - O'Grady, A.
AU - Caiazza, F.
AU - Heetun, Z.
AU - Mills, K. H.G.
AU - Sheahan, K.
AU - Ryan, E. J.
AU - Doherty, G. A.
AU - Kay, E.
AU - Creagh, E. M.
N1 - Publisher Copyright:
© 2015 The Authors Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - Caspases
KW - Colorectal cancer
KW - Inflammation
KW - Inflammatory bowel disease
UR - http://www.scopus.com/inward/record.url?scp=84930678168&partnerID=8YFLogxK
U2 - 10.1111/cei.12617
DO - 10.1111/cei.12617
M3 - Article
C2 - 25943872
AN - SCOPUS:84930678168
SN - 0009-9104
VL - 181
SP - 39
EP - 50
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 1
ER -