Mitogen-activated protein kinase phosphatase 1 (MKP-1) in macrophage biology and cardiovascular disease. A redox-regulated master controller of monocyte function and macrophage phenotype

Free Radic Biol Med. 2017 Aug:109:75-83. doi: 10.1016/j.freeradbiomed.2017.03.020. Epub 2017 Mar 19.

Abstract

MAPK pathways play a critical role in the activation of monocytes and macrophages by pathogens, signaling molecules and environmental cues and in the regulation of macrophage function and plasticity. MAPK phosphatase 1 (MKP-1) has emerged as the main counter-regulator of MAPK signaling in monocytes and macrophages. Loss of MKP-1 in monocytes and macrophages in response to metabolic stress leads to dysregulation of monocyte adhesion and migration, and gives rise to dysfunctional, proatherogenic monocyte-derived macrophages. Here we review the properties of this redox-regulated dual-specificity MAPK phosphatase and the role of MKP-1 in monocyte and macrophage biology and cardiovascular diseases.

Keywords: Atherosclerosis; DUSP; MAPK; Macrophage; Monocyte; Redox signaling.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Atherosclerosis / enzymology*
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Cell Adhesion
  • Cell Movement
  • Dual Specificity Phosphatase 1 / genetics
  • Dual Specificity Phosphatase 1 / metabolism*
  • Gene Expression Regulation
  • Heart Failure / enzymology*
  • Heart Failure / genetics
  • Heart Failure / pathology
  • Humans
  • Macrophages / enzymology*
  • Macrophages / pathology
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Monocytes / enzymology*
  • Monocytes / pathology
  • Oxidation-Reduction
  • Phenotype
  • Signal Transduction
  • Stress, Physiological / genetics

Substances

  • Mitogen-Activated Protein Kinases
  • DUSP1 protein, human
  • Dual Specificity Phosphatase 1