Apoptosis or necrosis--colonic epithelial cell survival.
The organization of the colonic epithelium is directed towards maintaining a continuous layer of cells with functional maturity at the surface, with a constant supply of epithelial cells of sufficient maturity from the crypts. Cells die by shedding at the surface or by undergoing apoptosis in situ, followed by shedding or phagocytosis. The nature of the predominant form of cell death in the normal colon remains uncertain but probably involves more than one route. Death of abnormal cells in the crypt is an important process to prevent clonal expansion and tumour formation. Apoptosis of normal cells is largely secondary to the effects of exposure to luminal factors, such as short-chain fatty adds and surfactants; loss of cell-substratum adhesion (anoikis) in the surface compartment; or cytokine-, oxidant stress- or lymphocyte-mediated death in association with inflammation. In inflammatory bowel disease (IBD) cell death can directly or indirectly compromise barrier function, impair effective epithelial restitution, lead to loss of stem cells and regenerative capacity, and has relevance to carcinogenesis. Therapeutic targeting of cell death in IBD is a double-edged sword--promotion of cell survival may favour more effective healing for active inflammation, while promotion of apoptosis may be protective from carcinogenesis.