Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury.

Jieshi Xie,Weiyang Li,Lei Tian,Lin Yang,Le Yang,Liying Li

doi:10.1038/srep27665

Jieshi Xie, Weiyang Li + Show 4 more

Open Access

https://doi.org/10.1038/srep27665

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Journal: Scientific reports	Publication Date: Jun 8, 2016
Citations: 47	License type: CC BY 4.0

Affiliation: Capital Medical University

Abstract

Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation.

Highlights

Macrophage migration inhibitor factor (MIF), named as such because of its ability to prevent random migration of macrophages, is an important cytokine, and was described almost 50 years ago[8,9]
CXCR2 and CXCR4 act as coreceptors of CD74, whereas CD74/CXCR2 and CD74/CXCR4 complexes are more inclined to contribute to MIF-mediated monocyte chemotaxis[9]
Hepatocytic MIF expression was upregulated upon mouse acute liver injury

Summary

Introduction

Macrophage migration inhibitor factor (MIF), named as such because of its ability to prevent random migration of macrophages, is an important cytokine, and was described almost 50 years ago[8,9]. Results Hepatocytic MIF expression was upregulated upon mouse acute liver injury. Immunofluorescent staining further confirmed that the expression of MIF and MCP-1 markedly increased in hepatocytes under 6 hours of LPS treatment (Fig. 2e).

Results

Conclusion