Available online 24 June 2022, 104575
Highlights•Methyl butyrate attenuates Con A-induced hepatitis and reduced the expression of inflammatory factors in the liver.
•Methyl butyrate inhibits the CXCL9-11/CXCR3 axis and affected the homing of Th1 cells to the liver in AIH mice.
•In vitro, methyl butyrate interferes with the stimulation of both human and mouse lymphocytes by Con A.
•Methyl butyrate downregulates TLR3 in the liver.
AbstractCon A-induced hepatitis is the most commonly used animal model for simulating autoimmune hepatitis (AIH). In this study, we investigated whether methyl butyrate (MB) alleviates Con A-induced hepatitis and how it affects Con A-stimulated lymphocytes. MB improves liver function in AIH mice, reducing the expression of several inflammatory cytokines and Th1 cell-associated chemokines in the liver, while significantly inhibiting toll-like receptor signaling pathway. Also in the liver, we verified that infiltrating Th1 cells were fewer after MB treatment. In vitro, we found that the activation of both human and mouse Th1 cells by Con A were inhibited by MB and the human-derived cells were even more sensitive. And MB caused a reduction in IFN-γ secretion together with TNF-α and IL-6. The above findings suggest that MB inhibits the activation and homing of Th1 cells to the liver, thereby attenuating Con A-induced liver injury, and may be a potential therapeutic agent for AIH.
KeywordsMethyl butyrate
autoimmune hepatitis
concanavalin A
interferon gamma
chemokines
toll-like receptor 3
AbbreviationsSCFAsshort-chain fatty acids
ALTalanine aminotransferase
ASTaspartate transaminase
PBMCsperipheral blood mononuclear cells
TNF-αtumor necrosis factor alpha
PLNperipheral lymph nodes
MLNmesenteric lymph nodes
KEGGKyoto Encyclopedia of Genes and Genomes
GSEAGene Set Enrichment Analysis
PPIprotein-protein interaction network
View full text© 2022 Published by Elsevier Inc.
留言 (0)