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Micro ‐RNA ‐155 Deficiency Prevents Alcohol‐Induced Serum Endotoxin Increase and Small Bowel Inflammation in Mice
Author(s) -
Lippai Dora,
Bala Shashi,
Catalano Donna,
Kodys Karen,
Szabo Gyongyi
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12483
Subject(s) - tumor necrosis factor alpha , medicine , endocrinology , inflammation , proinflammatory cytokine , alcohol , liquid diet , immune system , chemistry , immunology , biochemistry
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 (TNF α ) m RNA . 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 ( SHIP 1), TNF α , and nuclear factor‐ κ B ( NF ‐ κ B) were measured in proximal intestinal tissue. Endotoxin was measured in the serum. Results Acute alcohol binge enhanced, whereas chronic alcohol feeding decreased, Reg3b m RNA and protein levels in the SB. Both acute binge and chronic alcohol feeding increased serum endotoxin levels, intestinal NF‐ κ B activation and TNF α m RNA levels. However, TNF α 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 TNF α , and NF‐ κ B 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.