The Role and Mechanism of M2c Macrophages in Lipopolysaccharide/D-Galactosamine Induced Acute Hepatitis

Abstract

The study was based on the evaluation of the positive effect of M2c macrophages on liver tissue inflammation, pathological changes and tissue damage in lipopolysaccharide/D-galactosamine induced acute hepatitis. Meanwhile, whether M2c macrophages induced anti-inflammatory effects through Janus kinase/signal transducer and activator of transcription signaling pathway was also investigated. Forty institute of cancer research female mice in the same batch with no significant difference in body weight were distributed randomly into 5 different groups namely the control group, solvent control group, lipopolysaccharide/D-galactosamine, lipopolysaccharide/D-galactosamine+M2c and lipopolysaccharide/ D-galactosamine+M2c+ruxolitinib, 8 in each group. 6 h after the last treatment of mice in each group, serum was collected to detect the content of alanine aminotransferase and aspartate transferase. The pathology of liver tissue was determined using hematoxylineosin staining. The determination of the levels of expression of anti-inflammatory factors, pro-inflammatory factors, related apoptosis proteins and Janus kinase/signal transducer and activator of transcription signaling pathway related proteins in liver tissue were carried out by Western blot. After 6 h of induction with lipopolysaccharide/D-galactosamine, the liver function (alanine aminotransferase, aspartate aminotransferase), pathological score of liver slices, liver pro-inflammatory factors and anti-inflammatory factors (interleukin-6, tumor necrosis factor-alpha, interleukin-1beta and interleukin-10) were significantly improved in the mice blood. Comparative to the normal control group, apoptosis-related proteins (B-cell lymphoma-extra-large, B-cell lymphoma 2, Bcl-2- associated X protein) and other indicators were higher with a significant difference (p<0.05) under the acute hepatitis model induced lipopolysaccharide/D-galactosamine, after infusion of M2c macrophages from the tail vein of mice. The above indexes of mice were improved and exhibited a statistically significant difference (p<0.05). After adding ruxolitinib to intervene Janus kinase/signal transducer and activator of transcription signaling pathway on the basis of lipopolysaccharide/D-galactosamine+M2c group, the liver function, liver slice pathological score, pro and anti-inflammatory factor and apoptosis-related protein expressions were significantly higher as compared to the lipopolysaccharide/D-galactosamine+M2c group with significant difference (p<0.05), while the observed differences were not significant (p>0.05) in the lipopolysaccharide/ D-galactosamine group. Lipopolysaccharide/D-galactosamine induces the occurrence of acute hepatitis, which can well mimic the virus the pathogenic process of hepatitis. M2c macrophages exhibited a critical anti-inflammatory role in acute hepatitis via activating the Janus kinase/signal transducer and activator of transcription signaling pathway.