Induction of Macrophage M2b/c Polarization by Adipose Tissue-Derived Mesenchymal Stem Cells

J Immunol Res. 2019 Jun 19:2019:7059680. doi: 10.1155/2019/7059680. eCollection 2019.

Abstract

Background: Adipose-derived mesenchymal stem cells (ADMSCs) can promote healing and inhibit inflammation/immune response in local tissues, while the detailed mechanism remains unknown.

Results: ADMSCs and peritoneal macrophages were collected from C57BL/6 mice. The culture medium (CM) from ADMSCs (24 hours cultured) was collected. The CM was added to the Mφ culture system with lipopolysaccharide (LPS) or IL-4/IL-13 or blank. And those Mφ cultures without adding CM were used as controls. A series of classification markers and signaling pathways for Mφ polarization were detected by using flow cytometry, RT-PCR, and western blotting. Furthermore, the cell viability of all the groups was detected by CCK8 assay. After CM induction in different groups, M1-Mφ markers and M2a-Mφ were decreased; however, M2b/c-Mφ markers increased. STAT3/SOCS3 and STAT6/IRF4 were suppressed in all 3 CM-treated groups. Moreover, the cell viability of all 3 groups which were induced by CM significantly increased as compared to that of the control groups without adding CM.

Conclusion: ADMSCs can induce nonactivated macrophage and M1-Mφ into M2b/c-Mφ. Downregulation of the STAT3 and STAT6 pathway may involve in this process. This data shows that the anti-inflammatory role of ADMSC in local tissues may be partly due to their effect on Mφ to M2b/c-Mφ.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Cell Differentiation / immunology
  • Cell Survival
  • Inflammation
  • Interferon Regulatory Factors / metabolism
  • Interleukin-13 / pharmacology
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • STAT3 Transcription Factor / metabolism
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling 3 Protein / metabolism

Substances

  • Interferon Regulatory Factors
  • Interleukin-13
  • Lipopolysaccharides
  • STAT3 Transcription Factor
  • STAT6 Transcription Factor
  • Socs3 protein, mouse
  • Stat3 protein, mouse
  • Stat6 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • interferon regulatory factor-4
  • Interleukin-4