Abstract
Inflammatory bowel disease (IBD) is characterized by an exaggerated immune response that involves pro-inflammatory cytokines including IL-8. Production of these pro-inflammatory cytokines is triggered by pathogen-associated molecular patterns (PAMP). Butyrate, a product of bacterial fermentation of carbohydrates, has been reported to modulate inflammation in IBD, possibly by regulating production of pro-inflammatory cytokines. However, this effect of butyrate is controversial. In this study, we used Pam3CSK4 (Pam3CysSerLys4), the acylated NH2-terminus of the bacterial lipoprotein (a PAMP), to mimic in vivo infection of pathogens. Butyrate transiently down-regulated expression of IL-8 stimulated by Pam3CSK4. Treatment of cells with butyrate before Pam3CSK4, however, enhanced production of IL-8. Furthermore, butyrate induced expression of A20, a negative regulator of the nuclear factor-kappaB pathway. Over-expression of A20 inhibited Pam3CSK4-triggered IL-8 expression. Our data suggest that the inflammatory modulation of butyrate in IBD is mediated by A20 and a short pulse rather than continuous administration of butyrate may provide a protective effect on IBD.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents / therapeutic use
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Butyrates / pharmacology*
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Butyrates / therapeutic use
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Caco-2 Cells
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DNA-Binding Proteins
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Dose-Response Relationship, Drug
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Gastrointestinal Agents / pharmacology*
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Gastrointestinal Agents / therapeutic use
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Humans
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I-kappa B Proteins / metabolism
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Inflammatory Bowel Diseases / drug therapy
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Inflammatory Bowel Diseases / metabolism
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Interleukin-8 / metabolism*
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Intestinal Mucosa / drug effects*
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Intestinal Mucosa / metabolism
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Intestines / drug effects*
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Intestines / embryology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Lipopeptides
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Organ Culture Techniques
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Peptides / metabolism*
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Phosphorylation
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Time Factors
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Transfection
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Tumor Necrosis Factor alpha-Induced Protein 3
Substances
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Anti-Inflammatory Agents
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Butyrates
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DNA-Binding Proteins
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Gastrointestinal Agents
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I-kappa B Proteins
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Interleukin-8
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Intracellular Signaling Peptides and Proteins
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Lipopeptides
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NF-kappa B
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NFKBIA protein, human
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Nuclear Proteins
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Pam(3)CSK(4) peptide
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Peptides
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NF-KappaB Inhibitor alpha
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TNFAIP3 protein, human
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Tumor Necrosis Factor alpha-Induced Protein 3