Distinct Protein Expression Networks are Activated in Microglia Cells after Stimulation with IFN-γ and IL-4

Cells. 2019 Jun 12;8(6):580. doi: 10.3390/cells8060580.

Abstract

Microglia cells are the primary immune population of the central nervous system with a role in the regulation of several physiological and pathological conditions. Upon appropriate stimulation, microglia cells can be polarized in a pro-inflammatory M1-like or anti-inflammatory M2-like status. Biological processes and pathways engaged in microglia polarization are starting to be elucidated. To help clarify this, we used a liquid chromatography-mass spectrometry (LC-MS/MS) label free approach to characterize the proteomic profile of human microglia cell line (CHME-5) stimulated with gamma-interferon (IFN-γ) and interleukin-4 (IL-4) to induce a M1 or M2 phenotype, respectively. Outside the classical M1/M2 polarization markers, the M1 status appears to center around the activation of a classical inflammatory response and through the activation of multiple signaling pathways. M2 polarization resulted in a different pattern of protein modulation related to RNA and cellular metabolic processes. Together, our findings provide information regarding the protein changes specific to M1 and M2 activation states, and potentially link the polarization of microglia cells to the acquisition of a specific proteomic profile.

Keywords: IFN-γ; IL-4; mass spectrometry; microglia; microglia plasticity; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Interferon-gamma / pharmacology*
  • Interleukin-4 / pharmacology*
  • Macrophage Activation / drug effects
  • Metabolic Networks and Pathways / drug effects
  • Microglia / drug effects
  • Microglia / metabolism*
  • Phenotype
  • Proteins / metabolism*
  • Proteomics
  • Signal Transduction / drug effects
  • Transcription, Genetic / drug effects

Substances

  • Proteins
  • Interleukin-4
  • Interferon-gamma