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

CJ van der Woude*, JH Kleibeuker, PLM Jansen, H Moshage

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

94 Citations (Scopus)

Abstract

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-kappaBregulated genes e.g. a shift in the balance of pro- and anti-apoptotic genes towards a more antiapoptotic 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).

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalApoptosis
Volume9
Issue number2
Publication statusPublished - Mar-2004

Keywords

  • apoptosis
  • COX-2
  • gastro-intestinal tract
  • iNOS
  • NF-kappa B
  • NITRIC-OXIDE SYNTHASE
  • FACTOR-KAPPA-B
  • HELICOBACTER-PYLORI INFECTION
  • DYSPLASIA-CARCINOMA-SEQUENCE
  • BCL-2 PROTEIN EXPRESSION
  • HUMAN GASTRIC-CARCINOMA
  • TUMOR-NECROSIS-FACTOR
  • HIGH-GRADE DYSPLASIA
  • BARRETTS-ESOPHAGUS
  • ULCERATIVE-COLITIS

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