title: Micro-RNA-155 deficiency prevents alcohol-induced serum endotoxin increase and small bowel inflammation in mice.
abstract: BACKGROUND
  Chronic alcohol impairs gut barrier function and induces inflammatory cytokines. The effects of acute alcohol binge on the gut are partially understood. Micro-RNA-155 (miR-155), a modulator of cytokine and T-cell immune response in the gut, stabilizes tumor necrosis factor-α (TNFα) mRNA. Here, we investigated the role of the inflammation modulator miR-155 as well as the effects of acute binge and chronic alcohol feeding in the small bowel (SB) in mice.
  
  
  METHODS
  For the acute alcohol binge, wild-type (WT) mice received 5 g/kg 50% alcohol/d or equal amount of water oral gavage for 3 days. WT and miR-155-deficient (miR-155-knockout [KO]) mice received ethanol containing Lieber-DeCarli or isocaloric control diet for 5 weeks. MiR-155, antimicrobial peptide, regenerating islet-derived 3-beta (Reg3b), inflammation markers, Src homology 2-containing inositol phosphatase-1 (SHIP1), TNFα, and nuclear factor-κB (NF-κB) were measured in proximal intestinal tissue. Endotoxin was measured in the serum.
  
  
  RESULTS
  Acute alcohol binge enhanced, whereas chronic alcohol feeding decreased, Reg3b mRNA and protein levels in the SB. Both acute binge and chronic alcohol feeding increased serum endotoxin levels, intestinal NF-κB activation and TNFα mRNA levels. However, TNFα protein and miR-155 were increased only after chronic alcohol feeding in the SB. Furthermore, miR-155-KO mice were protected from chronic alcohol-induced increase in serum endotoxin, intestinal TNFα, and NF-κB activation. Also, alcohol-fed miR-155-KO mice had no decrease of Reg3b and SHIP1 levels.
  
  
  CONCLUSIONS
  These results demonstrate that both acute binge and chronic ethanol administration result in increased serum-endotoxin levels. Our study identifies a novel role for miR-155 in chronic alcohol-induced intestinal inflammation and barrier dysfunction.
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Dora
authors.initials: D
authors.lastname: Lippai
authors.forename: Shashi
authors.initials: S
authors.lastname: Bala
authors.forename: Donna
authors.initials: D
authors.lastname: Catalano
authors.forename: Karen
authors.initials: K
authors.lastname: Kodys
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Szabo
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D004731:Endotoxins / Q000097:blood*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000072181:Inositol Polyphosphate 5-Phosphatases; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016328:NF-kappa B; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490253:Reg3b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: Binge Drinking; Ethanol; Gut Barrier; Proximal Intestine; Tumor Necrosis Factor-α