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Gut. Apr 1998; 42(4): 477–484.
PMCID: PMC1727068

Activation of nuclear factor κB in inflammatory bowel disease


Background—Expression of pro-inflammatory cytokines is increased in the intestinal lamina propria of patients with inflammatory bowel disease (IBD). Nuclear factor κB (NFκB) controls transcription of inflammation genes. On activation, NFκB is rapidly released from its cytoplasmic inhibitor (IκB), transmigrates into the nucleus, and binds to DNA response elements in gene promoter regions.
Aims—To investigate whether increased activation of NFκB is important in IBD and may be down-regulated by anti-inflammatory treatment.
Methods—Activation of NFκB was determined by western blot assessment and electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as lamina propria mononuclear cells.
Results—Nuclear levels of NFκB p65 are increased in lamina propria biopsy specimens from patients with Crohn's disease in comparison with patients with ulcerative colitis and controls. Increased activation of NFκB was detected in lamina propria mononuclear cells from patients with active IBD. Corticosteroids strongly inhibit intestinal NFκB activation in IBD in vivo and in vitro by stabilising the cytosolic inhibitor IκBα against activation induced degradation.
Conclusions—In both IBDs, but particularly Crohn's disease, increased activation of NFκB may be involved in the regulation of the inflammatory response. Inhibition of NFκB activation may represent a mechanism by which steroids exert an anti-inflammatory effect in IBD.

Keywords: interleukin 1ß; inflammatory bowel disease; intestinal immunity; signal transduction; steroids; tumour necrosis factor α

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Selected References

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Figures and Tables

Figure 1
NFκB p65 in nuclear extracts from colonic biospsy samples. Colonic biopsy specimens from 10 patients with active Crohn's disease (CD), 14 patients with active ulcerative colitis (UC), six disease specificity controls (DSC), and seven normal controls ...
Figure 2
Total NFκB p65 and IκBα in colonic biospy tissue. Colonic biopsy specimens were homogenised and analysed by western blot without prior compartmentalised extraction. Densitometric readings are shown by the bar graph (mean (SD)). ...
Figure 3
Detection of NFκB in the intestinal lamina propria. (A) Nuclear extracts were prepared from colonoscopic biopsy specimens. A representative radioactive electrophoretic mobility shift assay using consensus oligonucleotides to detect NFκ ...
Figure 4
Inhibition of NFκB activation (A) and IκBα degradation (B) by steroids (dexamethasone) and N-α-tosyl-phenylalanine chloromethyl ketone (TPCK). Nuclear extracts were prepared from lamnia propria mononuclear cells obtained ...
Figure 5
Nuclear NFκB p65 from colonoscopic biopsy specimens from patients with inflammatory bowel disease is decreased by steroid treatment. Sigmoid biopsy specimens were obtained from patients with moderately to highly active ileocolonic Crohn's disease ...
Figure 6
Schematic representation of NFκB activation and inhibition by steroids. Activating stimuli including tumour necrosis factor α (TNF-α) and lipopolysaccharide (LPS) promote degradation of IκBα and the subsequent release ...

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