An insight into the role of magnesium in the immunomodulatory properties of mesenchymal stem cells

J Nutr Biochem. 2018 May:55:200-208. doi: 10.1016/j.jnutbio.2018.02.006. Epub 2018 Feb 13.

Abstract

Magnesium (Mg2+) is a mineral with the ability to influence cell proliferation and to modulate inflammatory/immune responses, due to its anti-inflammatory properties. In addition, mesenchymal stem cells (MSCs) modulate the function of all major immune cell populations. Knowing that, the current work aimed to investigate the effects of Mg2+ enrichment, and its influence on the immunomodulatory capacity of MSCs. Murine C3H/10T1/2 MSCs were cultivated in media with different concentrations of Mg2+ (0, 1, 3 and 5 mM), in order to evaluate the effects of Mg2+ on MSC immunomodulatory properties, cell proliferation rates, expression of NFκB and STAT-3, production of IL-1β, IL-6, TGF-β, IL-10, PGE2 and NO, and TRPM7 expression. The results showed that TRPM7 is expressed in MSCs, but Mg2+, in the way that cells were cultivated, did not affect TRPM7 expression. Additionally, there was no difference in the intracellular concentration of Mg2+. Mg2+, especially at 5 mM, raised proliferation rates of MSCs, and modulated immune responses by decreasing levels of IL-1β and IL-6, and by increasing levels of IL-10 and PGE2 in cells stimulated with LPS or TNF-α. In addition, MSCs cultured in 5 mM Mg2+ expressed lower levels of pNFκB/NFκB and higher levels of pSTAT-3/STAT-3. Furthermore, conditioned media from MSCs reduced lymphocyte and macrophage proliferation, but Mg2+ did not affect this parameter. In addition, conditioned media from MSCs cultured at 5 mM of Mg2+ modulated the production profile of cytokines, especially of IL-1β and IL-6 in macrophages. In conclusion, Mg2+ is able to modulate some immunoregulatory properties of MSCs.

Keywords: Cytokines; Immunomodulation; Macrophages and lymphocytes; Magnesium; Mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Dinoprostone / metabolism
  • Immunomodulation
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Macrophages / cytology
  • Macrophages / metabolism
  • Magnesium / pharmacology
  • Magnesium / physiology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology*
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • STAT3 Transcription Factor / metabolism
  • TRPM Cation Channels / metabolism

Substances

  • Culture Media, Conditioned
  • Cytokines
  • NF-kappa B
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • TRPM Cation Channels
  • Nitric Oxide
  • Trpm7 protein, mouse
  • Magnesium
  • Dinoprostone