Macrophage inflammatory protein-2 as mediator of inflammation in acute liver injury

World J Gastroenterol. 2017 May 7;23(17):3043-3052. doi: 10.3748/wjg.v23.i17.3043.

Abstract

Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2. MIP-2-recruited and activated neutrophils can accelerate liver inflammation by releasing various inflammatory mediators. Here, we give a brief introduction to the basic molecular and cellular sources of MIP-2, and focus on its physiological and pathological functions in acute liver injury induced by concanavalin A, lipopolysaccharides, irradiation, ischemia/reperfusion, alcohol, and hypoxia, and hepatectomy-induced liver regeneration and tumor colorectal metastasis. Further understanding of the regulatory mechanisms of MIP-2 secretion and activation may be helpful to develop MIP-2-targeted therapeutic strategies to prevent liver inflammation.

Keywords: Inflammation; Liver injury; Macrophage inflammatory protein-2; Macrophages; Polymorphonuclear neutrophils.

Publication types

  • Review

MeSH terms

  • Chemical and Drug Induced Liver Injury / pathology*
  • Chemokine CXCL2 / metabolism*
  • Chemokines, CXC / metabolism*
  • Epithelial Cells / metabolism
  • Hepatitis / etiology
  • Hepatitis / immunology
  • Hepatitis / pathology*
  • Hepatocytes / metabolism
  • Humans
  • Kupffer Cells / metabolism*
  • Liver / cytology
  • Liver / pathology
  • Liver / physiology
  • Liver Regeneration*
  • MAP Kinase Signaling System
  • Neutrophil Infiltration
  • Neutrophils / metabolism
  • Radiotherapy / adverse effects
  • Receptors, Interleukin-8A / metabolism
  • Receptors, Interleukin-8B / metabolism
  • Tumor Necrosis Factor-alpha

Substances

  • CXCL2 protein, human
  • CXCL3 protein, human
  • Chemokine CXCL2
  • Chemokines, CXC
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Tumor Necrosis Factor-alpha