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Inflammatory bowel disease
Butyrate inhibits inflammatory responses through NFκB inhibition: implications for Crohn's disease

Abstract

BACKGROUND/AIM Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NFκB), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression.

METHODS Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NFκB p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NFκB inhibitory protein (IκBα) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis.

RESULTS Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NFκB from the cytoplasm to the nucleus. LPS induced NFκB transcriptional activity was decreased by butyrate while IκBα levels were stable. Butyrate treatment also improved TNBS induced colitis.

CONCLUSIONS Butyrate decreases proinflammatory cytokine expression via inhibition of NFκB activation and IκBα degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.

  • inflammation
  • butyrate
  • Crohn's disease
  • nuclear factor kappa B
  • cytokines

  • Abbreviations used in this paper

    CD
    Crohn's disease
    IBD
    inflammatory bowel disease
    TNF
    tumour necrosis factor
    IL
    interleukin
    TNBS
    trinitrobenzene sulphonic acid
    LPS
    lipopolysaccharide
    PBMC
    peripheral blood mononuclear cells
    LPMC
    lamina propria mononuclear cells
    NFκB
    nuclear factor kappa B
    IκB
    inhibitor protein kappa B
    RT-PCR
    reverse transcription-polymerase chain reaction
    TSA
    trichostatin A

    • https://doi.org/10.1136/gut.47.3.397

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