Chronic inflammation, apoptosis and (pre-)malignant lesions in the gastro-intestinal tract.
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).
van der Woude
C J
CJ
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands. c.vanderwoude@erasmusmc.nl
Kleibeuker
J H
JH
Jansen
P L M
PL
Moshage
H
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051546:Cyclooxygenase 2; D005770:Gastrointestinal Neoplasms / Q000503:physiopathology*; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases