Title:Epigenetic Modifications of the Nuclear Factor Kappa B Signalling Pathway and its Impact on Inflammatory Bowel Disease
Volume: 27
Issue: 35
Author(s): Stamatia Papoutsopoulou*Barry J. Campbell*
Affiliation:
- Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, L69 3GE,United Kingdom
- Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, L69 3GE,United Kingdom
Keywords:
Epigenetics, NF-κB, inflammation, intestine, Crohn's disease, ulcerative colitis, colon cancer.
Abstract:
Background: Inflammatory bowel disease (IBD) is a multifactorial condition influenced by the immune
system, the intestinal microbiota, environmental factors, genetic and epigenetic factors. Genetic- and environment-
induced dysregulation of the Nuclear Factor-kappa B (NF-κB) transcription factor pathway has been
linked to IBD pathogenesis.
Objective: To assess the current evidence in relation to the contribution of the classical and alternative NF-κB
pathways in IBD and to discuss the epigenetic mechanisms that impact on NF-κB function.
Methods: A Medline search for ‘NF-kappaB/NF-κB’, in combination with terms including ‘inflammatory bowel
disease/IBD’, 'intestinal inflammation', ‘Crohn's disease’, ‘ulcerative colitis’, 'colitis'; ‘epigenetics’, ‘DNA
methylation’, ‘histones’, ‘microRNAs/miRNAs’ and ‘short non-coding/long non-coding RNAs’ was performed.
Results: Both NF-κB pathways contribute to the chronic inflammation underlying IBD by regulating the inflammatory
immune responses and homeostasis of the intestinal epithelium (classical pathway) or regulating bowel
inflammation and epithelial microfold (M) cell function (alternative pathway). DNA methylation is a common
epigenetic modification in intestinal inflammation, including NFKB1 and RELA loci. Conversely, little is understood
regarding epigenetic effects on genes encoding other NF-κB subunits, particularly those of the alternative
pathway, and in the context of IBD. However, NF-κB interaction with chromatin modifiers is also seen to be an
essential mechanism of regulation of downstream target genes relevant to NF-κB-mediated inflammatory responses.
Conclusion: Further research is clearly warranted in this area, as understanding the cell-specific regulation of
the NF-κB pathways will bring researchers into a position to achieve more efficient stratification of IBD patients,
and more targeted and effective choice of treatment.
