Methyl butyrate attenuates concanavalin A-induced autoimmune hepatitis by inhibiting Th1-cell activation and homing to the liver

Elsevier

Available online 24 June 2022, 104575

Cellular ImmunologyHighlights•

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.

Abstract

Con 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.

Keywords

Methyl butyrate

autoimmune hepatitis

concanavalin A

interferon gamma

chemokines

toll-like receptor 3

AbbreviationsSCFAs

short-chain fatty acids

ALT

alanine aminotransferase

AST

aspartate transaminase

PBMCs

peripheral blood mononuclear cells

TNF-α

tumor necrosis factor alpha

PLN

peripheral lymph nodes

MLN

mesenteric lymph nodes

KEGG

Kyoto Encyclopedia of Genes and Genomes

GSEA

Gene Set Enrichment Analysis

PPI

protein-protein interaction network

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© 2022 Published by Elsevier Inc.

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