Butyrate regulates the expression of pathogen-triggered IL-8 in intestinal epithelia.
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.
Weng
Meiqian
M
Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Walker
W Allan
WA
Sanderson
Ian R
IR
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002087:Butyrates / Q000494:pharmacology* / Q000627:therapeutic use; D018938:Caco-2 Cells; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D055666:Lipopeptides; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D013997:Time Factors; D014162:Transfection; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3