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


CONCLUSIONS
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.
Clinical Research Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. yanghaiwei2002@yahoo.com.cn
Haiwei
H
Yang
Jifu
J
Wei
Huiyun
H
Zhang
Liyan
L
Lin
Wei
W
Zhang
Shaoheng
S
He
D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
D016207:Cytokines; D018793:Interleukin-13; D015850:Interleukin-6; D008562:Membrane Glycoproteins; C495344:TLR3 protein, human; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D016178:Granulocyte-Macrophage Colony-Stimulating Factor