TLR-induced immunomodulatory cytokine expression by human gingival stem/progenitor cells

Cell Immunol. 2018 Apr:326:60-67. doi: 10.1016/j.cellimm.2017.01.007. Epub 2017 Jan 10.

Abstract

During therapeutic application, mesenchymal stem cells (MSCs) may interact with their environment via their expressed toll-like-receptors (TLRs) leading to pro- or anti-inflammatory immune responses. The present study aimed to describe the gingival margin-derived stem/progenitor cells' (G-MSCs) TLR-induced immune regulatory response to specific TLR agonists. Gingival cells were obtained, immunomagnetically sorted via anti-STRO-1 antibodies and seeded out to achieve colony forming units (CFUs). G-MSCs were investigated for stem cell characteristics and TLR expression. Specific TLR agonists were applied and m-RNA expression of pro- and anti-inflammatory factors was analyzed via real-time polymerase chain reaction. G-MSCs showed all characteristics of stem/progenitor cells. All TLR agonists induced pro-inflammatory cytokines, except for the TLR3 agonist, which significantly promoted the anti-inflammatory response. (p⩽0.05, Wilcoxon-Signed-Ranks-Test). TLR-induced immunomodulation by G-MSCs could impact their therapeutic potential in vivo. Two distinctive pro-inflammatory and an anti-inflammatory TLR-induced phenotypes of G-MSCs become noticeable in this study.

Keywords: Gingiva; Immunomodulation; Inflammation; Polymerase chain reaction; Stem cells; Toll-like receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Gingiva / cytology
  • Humans
  • Immunomodulation / immunology*
  • Lipopeptides / pharmacology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism
  • Poly I-C / pharmacology
  • Toll-Like Receptor 3 / agonists
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / immunology*
  • Toll-Like Receptors / metabolism

Substances

  • Cytokines
  • Lipopeptides
  • Pam(3)CSK(4) peptide
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Poly I-C