Chronic inflammation, apoptosis and (pre-)malignant lesions in the gastro-intestinal tract

Apoptosis. 2004 Mar;9(2):123-30. doi: 10.1023/B:APPT.0000018794.26438.22.


Inflammatory conditions are characterized by activation of the transcription factor nuclear factor kappa B (NF-kappaB), resulting in the expression of NF-kappaB-regulated, inflammation-related genes, such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). Expression of these genes contributes to the survival of cells. Indeed, exposure to pro-inflammatory cytokines in the absence of NF-kappaB activation leads to apoptosis.(1,2) Chronic inflammatory conditions are accompanied by constitutive activation of NF-kappaB and hence, to the continuous expression of pro-survival genes, as has been observed in chronic gastritis.(3) Although beneficial for the survival of cells during exposure to inflammatory stress, the continuous activation of NF-kappaB may also pose a risk: cells with a pro-survival phenotype may give rise to continuously proliferating cells and may thus be tumorigenic. Progression to a malignant phenotype of these cells will most likely involve additional changes in the expression of non-NF-kappaB regulated genes e.g. a shift in the balance of pro- and anti-apoptotic genes towards a more anti-apoptotic phenotype. Literature on inflammation-related genes and the apoptotic balance in pre-malignant and malignant conditions in the gastro-intestinal tract is still scarce and conflicting. In this review, we aim to give an overview of the existing literature and we will focus on inflammation- and apoptosis-related genes in the sequence of normal epithelium-inflamed epithelium-metaplasia-dysplasia-cancer in the gastrointestinal tract, in particular esophagus (Barrett's esophagus: BE), stomach (gastritis) and colon (inflammatory bowel disease: IBD).

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cyclooxygenase 2
  • Gastrointestinal Neoplasms / physiopathology*
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / physiopathology*
  • Humans
  • Inflammation / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Isoenzymes / metabolism
  • Membrane Proteins
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases / metabolism


  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases