Stimulation of autophagy prevents intestinal mucosal inflammation and ameliorates murine colitis

British Journal of Pharmacology
Dulce C Macias-CejaMaría D Barrachina

Abstract

Defective autophagy contributes to the pathogenesis of inflammatory disorders such as inflammatory bowel disease and there are interactions between autophagy and inflammation. Here we have analysed the effects of autophagy stimulators on murine colitis. Mice were treated with intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) (3.5 mg·20 g-1 ) and body weight was measured daily. Histological damage was scored 2 or 4 days after treatment. Some mice received trehalose (3% in drinking water 3 weeks before TNBS administration) or a daily administration of rapamycin (1.25 mg·kg-1 , i.p.), betanin (1 g·kg-1 , i.p.) or betanin + 3-methyladenine (3MA) (10 mg·kg-1 , i.p.). Protein levels of p-mTOR, p62, LC3, BCL10, NFκB, IκBα and p-IκBα in mucosa were determined by Western blots and mRNA expression of TNFα, IL1β, IL6, IL10, COX2, CCR7, CD11c, inducible NOS and CD86 by qRT-PCR. Impaired autophagy associated with body weight loss and intestinal damage was detected in the mucosa of TNBS-treated mice. Administration of trehalose, rapamycin or betanin prevented the impaired autophagic flux induced by TNBS and decreased mucosal protein levels of BCL10, p-IκBα and NFκB-p65 and the expression of pro-inflammatory cytokines an...Continue Reading

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Citations

Feb 28, 2018·Clinical & Translational Immunology·Bram VerstocktJames C Lee
Feb 13, 2019·Cells·Young Jin JangSanguine Byun
Jul 31, 2019·Journal of Crohn's & Colitis·Dolores Ortiz-MasiàMaría D Barrachina
Feb 16, 2019·Journal of Biomedical Science·Sabah HaqWaliul I Khan
Jun 12, 2019·Journal of Immunology Research·Angélica Y Gómez-ArauzGuillermo Meléndez
Oct 4, 2018·Mucosal Immunology·Dulce C Macias-CejaMaría D Barrachina
May 13, 2020·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Miklós ConstantinovitsGyörgyi Műzes
Sep 22, 2019·Cells·Jesus Cosin-RogerSara Calatayud
Dec 10, 2020·Journal of Periodontal Research·Yun YuanHui Huang
Sep 3, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Lei GeKehe Huang
Apr 7, 2019·Trends in Molecular Medicine·Sruthi Vijaya Retnakumar, Sylviane Muller
Jun 25, 2021·Cellular and Molecular Gastroenterology and Hepatology·Aaron K ChowBrian D Gulbransen

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