| First Author | Lippai D | Year | 2014 |
| Journal | Alcohol Clin Exp Res | Volume | 38 |
| Issue | 8 | Pages | 2217-24 |
| PubMed ID | 25156614 | Mgi Jnum | J:331339 |
| Mgi Id | MGI:6862686 | Doi | 10.1111/acer.12483 |
| Citation | Lippai D, et al. (2014) Micro-RNA-155 deficiency prevents alcohol-induced serum endotoxin increase and small bowel inflammation in mice. Alcohol Clin Exp Res 38(8):2217-24 |
| abstractText | 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. |
