Splenectomy Promotes Macrophage Polarization in a Mouse Model of Concanavalin A- (ConA-) Induced Liver Fibrosis.

Abstract:

Background:Splenectomy can improve liver function and survival in patients with autoimmune hepatitis (AIH) and liver cirrhosis. We investigated the underlying mechanism in a mouse model of concanavalin A- (ConA-) induced liver fibrosis. Methods:We used ConA to induce immune liver fibrosis in BALB/c mice. Splenectomy was performed alone or with the administration of dexamethasone (DEX). Changes in blood and liver tissues were evaluated. Results:Mice treated with ConA for 7 weeks developed advanced liver fibrosis, while splenectomy suppressed liver fibrosis. Although the populations of macrophages/monocytes and M1 macrophages decreased after splenectomy, the inflammatory factors associated with M2 macrophages increased after splenectomy. Furthermore, the population of circulating CD11b+Ly6Chigh myeloid-derived suppressor cells (MDSCs) increased after splenectomy. After ConA treatment, elevated levels of activated and total NF-kBp65/p50 combined with DNA were observed in hepatic tissues. In contrast, the levels of NF-κB p65/p50 decreased after splenectomy. Conclusions:Splenectomy may promote the polarization of CD11b+Ly6Chigh MDSCs and the differentiation of M2 macrophages while restricting the level of NF-κB p65-p50 heterodimers. These factors may suppress the progression of liver fibrosis.

journal_name

Biomed Res Int

authors

Wang Y,Guo X,Jiao G,Luo L,Zhou L,Zhang J,Wang B

doi

10.1155/2019/5756189

subject

Has Abstract

pub_date

2019-01-06 00:00:00

pages

5756189

eissn

2314-6133

issn

2314-6141

journal_volume

2019

pub_type

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