Журнал клинической и клеточной иммунологии
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Inflammatory Mediators Contributing to Intestinal Epithelial Cell Apoptosis and Barrier Disruption in IBD

Michael Schnoor and Nancy A. Louis

In Crohn’s Disease (CD) and ulcerative colitis (UC), the major manifestations of inflammatory bowel disease (IBD), genetically predisposed individuals develop chronic intestinal inflammation in response to environmental stimuli, which are mainly derived from luminal flora. Intestinal responses to luminal flora breaching the intestinal barrier require cytokine-regulated activation of elements of innate and acquired immunity, leading to a targeted and contained inflammatory response. Recent population-based genetic analyses have identified polymorphisms in specific genes relevant to pathways critical for inflammatory signalling and cellular response to stress as carrying increased risk for the development of either CD or UC. Specifically, key mediators of apoptosis and autophagy are implicated in the genetic vulnerability to IBD. Patients with IBD have a compromise of their intestinal barrier integrity, as do their first-degree relatives even in the absence of clinical disease, underscoring the critical nature of barrier integrity in the prevention of aberrant immune responses to intestinal flora. Here we explore the relationships between two of the key proinflammatory cytokines mediating intestinal inflammation in IBD, TNF-α and IFNγ, and the mechanisms by which they regulate epithelial apoptosis and intestinal barrier. Specifically we review factors regulating the balance between pro- and antiapoptotic stimuli resulting from the activation of NF-κB and Aktdependent signalling by proinflammatory cytokines, as well as the influence of oxygen tension and nutritional factors on these pathways.