Show simple item record

dc.contributor.authorLippai, Dora
dc.contributor.authorBala, Shashi
dc.contributor.authorCatalano, Donna
dc.contributor.authorKodys, Karen
dc.contributor.authorSzabo, Gyongyi
dc.date2022-08-11T08:08:36.000
dc.date.accessioned2022-08-23T16:01:13Z
dc.date.available2022-08-23T16:01:13Z
dc.date.issued2014-08-01
dc.date.submitted2014-09-11
dc.identifier.citationAlcohol Clin Exp Res. 2014 Aug;38(8):2217-24. doi: 10.1111/acer.12483. <a href="http://dx.doi.org/10.1111/acer.12483">Link to article on publisher's site</a>
dc.identifier.issn0145-6008 (Linking)
dc.identifier.doi10.1111/acer.12483
dc.identifier.pmid25156614
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31069
dc.description.abstractBACKGROUND: 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25156614&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1111/acer.12483
dc.subjectDigestive System Diseases
dc.subjectGastroenterology
dc.subjectGenomics
dc.subjectHepatology
dc.subjectImmunopathology
dc.subjectSubstance Abuse and Addiction
dc.titleMicro-RNA-155 Deficiency Prevents Alcohol-Induced Serum Endotoxin Increase and Small Bowel Inflammation in Mice
dc.typeJournal Article
dc.source.journaltitleAlcoholism, clinical and experimental research
dc.source.volume38
dc.source.issue8
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gastroenterology_pp/126
dc.identifier.contextkey6105451
html.description.abstract<p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p>
dc.identifier.submissionpathgastroenterology_pp/126
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology
dc.source.pages2217-24


This item appears in the following Collection(s)

Show simple item record