Micro-RNA-155 Deficiency Prevents Alcohol-Induced Serum Endotoxin Increase and Small Bowel Inflammation in Mice
Department of Medicine, Division of Gastroenterology
Digestive System Diseases | Gastroenterology | Genomics | Hepatology | Immunopathology | Substance Abuse and Addiction
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-alpha (TNFalpha) 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), TNFalpha, and nuclear factor-kappaB (NF-kappaB) 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-kappaB activation and TNFalpha mRNA levels. However, TNFalpha 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 TNFalpha, and NF-kappaB 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.
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Citation: Alcohol Clin Exp Res. 2014 Aug;38(8):2217-24. doi: 10.1111/acer.12483. Link to article on publisher's site
Lippai, Dora; Bala, Shashi; Catalano, Donna; Kodys, Karen; and Szabo, Gyongyi, "Micro-RNA-155 Deficiency Prevents Alcohol-Induced Serum Endotoxin Increase and Small Bowel Inflammation in Mice" (2014). Gastroenterology Publications and Presentations. 126.