Upregulation of Toll-like receptor (TLR) expression and release of cytokines from P815 mast cells by GM-CSF

BMC Cell Biol. 2009 May 9;10:37. doi: 10.1186/1471-2121-10-37.

Abstract

Background: Recently, mast cells have been recognized to express several Toll-like receptors (TLRs) on their membrane surfaces, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was reported to be able to alter expression of TLRs and cytokine production in neutrophils. However, whether GM-CSF modulates the expression of TLR and cytokine production in mast cells is not clear.

Results: Using flow cytometry and real time PCR techniques, we found that GM-CSF upregulated expression of TLR3 and TLR7 in P815 cells in a concentration dependent manner. GM-CSF also provoked approximately up to 2.4 and 2.3 fold increase in IL-13 and IL-6 release from P815 cells, respectively following 16 h incubation. GM-CSF induced IL-13 secretion, TLR3 and TLR7 expression appeared to be through activation of mitogen-activated protein kinase (MAPK) and phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathways, whereas GM-CSF elicited IL-6 release seemed via Akt signaling pathway. At 10 ng/ml, GM-CSF significantly enhanced R-848-induced IL-6 release from P815 cells.

Conclusion: The ability of GM-CSF in modulation of expression of TLR3 and TLR7 in P815 mast cells and in stimulation of IL-13 and IL-6 release from P815 mast cells in vitro suggests that GM-CSF might play an important role in enhancing the innate immune responses of mast cell to viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines / immunology*
  • Gene Expression
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Interleukin-13 / immunology
  • Interleukin-6 / immunology
  • Mast Cells / immunology*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Mice
  • Toll-Like Receptor 3 / genetics*
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 7 / genetics*
  • Toll-Like Receptor 7 / immunology
  • Up-Regulation*

Substances

  • Cytokines
  • Interleukin-13
  • Interleukin-6
  • Membrane Glycoproteins
  • TLR3 protein, human
  • Tlr7 protein, mouse
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • Granulocyte-Macrophage Colony-Stimulating Factor