Stimulation of autophagy prevents intestinal mucosal inflammation and ameliorates murine colitis

Autor:	P Salvador, Dolores Ortiz-Masiá, Juan V. Esplugues, Maria D. Barrachina, Sara Calatayud, Jesus Cosin-Roger, Dulce C Macias-Ceja, Carlos Hernández
Rok vydání:	2017
Předmět:	0301 basic medicine Pharmacology business.industry Autophagy Inflammation Stimulation medicine.disease Inflammatory bowel disease Pathogenesis 03 medical and health sciences IκBα chemistry.chemical_compound 030104 developmental biology chemistry Medicine Tumor necrosis factor alpha medicine.symptom business Betanin
Zdroj:	British Journal of Pharmacology. 174:2501-2511
ISSN:	0007-1188
DOI:	10.1111/bph.13860
Popis:	Background and pourpose A defective autophagy is involved in the pathogenesis of inflammatory disorders such as IBD. Cross talk interactions between autophagy and inflammation have been reported and we analyse the effects of autophagy stimulators on murine colitis. Experimental approach Mice were treated with intrarectal administration of TNBS (3.5 mg/20 g BW) and body weight was measured every day and histological damage score analysed two or four days after treatment. Some mice received trehalose (3% in drinking water three weeks before TNBS administration) or a daily administration of rapamycin (1.25 mg/kg, i.p.), betanin (1g/kg, i.p.) or betanin + 3MA (10mg/kg, i.p.). Mucosal protein levels of p-mTOR, p62, LC3, BCL10, NFκB, IκBα and p-IκBα were determined by WB and mRNA expression of TNFα, IL1β, IL6, IL10, COX2, CCR7, CD11c, iNOS and CD86 by qRT-PCR. Key results An 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 NFκBp65 and the expression of pro-inflammatory cytokines and M1 macrophage markers. Blockade of the autophagosome formation by treatment of mice with 3MA, prevented the reduction in protein levels of p62, BCL10, p-IκBα and NFκBp65 induced by betanin in TNBS-treated mice and weakened the protective effects of betanin on murine colitis. Conclusions and implications Our results demonstrate that pharmacological stimulation of mucosal autophagy reduces intestinal inflammation and ameliorates murine colitis.
Databáze:	OpenAIRE
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