CD14 dictates differential activation of mesenchymal stromal cells through AKT, NF-κB and P38 signals

Biosci Rep. 2019 Jul 5;39(7):BSR20190807. doi: 10.1042/BSR20190807. Print 2019 Jul 31.

Abstract

Mesenchymal stromal cells (MSCs) widely exist in many tissues and have multiple differentiation potential and immunomodulatory capacities. Recently, MSCs have become promising tools for the treatment of various degenerative disorders and autoimmune diseases. The properties of MSCs could be modified in different microenvironments. Thus, it is important to explore the factors controlling MSC function. The presence of Toll-like receptors (TLRs) in MSCs was demonstrated according to previous studies. Consistently, we also illustrated the expression of TLRs in both murine and human MSCs, and displayed that the expression patterns of TLRs in MSCs from different sources. Furthermore, we explored the role of TLR and TLR signaling pathway in MSCs. Interestingly, activation of TLR4-induced expression of cytokines and some specific genes in MSCs. However, MSCs retained much lower mRNA level compared with macrophages. We explored the expression of CD14 in MSCs from different sources, which played a vital role in TLR4 signaling pathway, and found that MSCs are almost negative for CD14. Moreover, only partial activation of TLR4 signaling pathway was observed in MSCs, with no activation of AKT, NF-κB and P38. Here, in the study we defined TLR expression, function and activation in MSCs, which is critical for designing MSC-based therapies.

Keywords: CD14; Mesenchymal stroma cells; TLRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Macrophages / drug effects
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • NF-kappa B / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction / genetics
  • Toll-Like Receptor 4 / genetics*
  • Transcription Factor RelA / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Lipopolysaccharide Receptors
  • NF-kappa B
  • RELA protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases