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Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential

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Abstract
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.
Keywords
colorectal cancer, inflammation, caspases, LIPOPOLYSACCHARIDE, MUCOSA, CELLS, CROHNS-DISEASE, MUTATIONAL ANALYSIS, inflammatory bowel disease, LOW-GRADE DYSPLASIA, ULCERATIVE-COLITIS, NLRP3 INFLAMMASOME, ACTIVATION, GENES

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Citation

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MLA
Flood, B et al. “Altered Expression of Caspases-4 and -5 During Inflammatory Bowel Disease and Colorectal Cancer : Diagnostic and Therapeutic Potential.” CLINICAL AND EXPERIMENTAL IMMUNOLOGY 181.1 (2015): 39–50. Print.
APA
Flood, B., Oficjalska, K., Laukens, D., Fay, J., O’Grady, A., Caiazza, F., Heetun, Z., et al. (2015). Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 181(1), 39–50.
Chicago author-date
Flood, B, K Oficjalska, Debby Laukens, J Fay, A O’Grady, F Caiazza, Z Heetun, et al. 2015. “Altered Expression of Caspases-4 and -5 During Inflammatory Bowel Disease and Colorectal Cancer : Diagnostic and Therapeutic Potential.” Clinical and Experimental Immunology 181 (1): 39–50.
Chicago author-date (all authors)
Flood, B, K Oficjalska, Debby Laukens, J Fay, A O’Grady, F Caiazza, Z Heetun, KHG Mills, K Sheahan, EJ Ryan, GA Doherty, E Kay, and EM Creagh. 2015. “Altered Expression of Caspases-4 and -5 During Inflammatory Bowel Disease and Colorectal Cancer : Diagnostic and Therapeutic Potential.” Clinical and Experimental Immunology 181 (1): 39–50.
Vancouver
1.
Flood B, Oficjalska K, Laukens D, Fay J, O’Grady A, Caiazza F, et al. Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential. CLINICAL AND EXPERIMENTAL IMMUNOLOGY. 2015;181(1):39–50.
IEEE
[1]
B. Flood et al., “Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential,” CLINICAL AND EXPERIMENTAL IMMUNOLOGY, vol. 181, no. 1, pp. 39–50, 2015.
@article{6849914,
  abstract     = {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.},
  author       = {Flood, B and Oficjalska, K and Laukens, Debby and Fay, J and O'Grady, A and Caiazza, F and Heetun, Z and Mills, KHG and Sheahan, K and Ryan, EJ and Doherty, GA and Kay, E and Creagh, EM},
  issn         = {0009-9104},
  journal      = {CLINICAL AND EXPERIMENTAL IMMUNOLOGY},
  keywords     = {colorectal cancer,inflammation,caspases,LIPOPOLYSACCHARIDE,MUCOSA,CELLS,CROHNS-DISEASE,MUTATIONAL ANALYSIS,inflammatory bowel disease,LOW-GRADE DYSPLASIA,ULCERATIVE-COLITIS,NLRP3 INFLAMMASOME,ACTIVATION,GENES},
  language     = {eng},
  number       = {1},
  pages        = {39--50},
  title        = {Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential},
  url          = {http://dx.doi.org/10.1111/cei.12617},
  volume       = {181},
  year         = {2015},
}

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