Abstract
BackgroudRecently, 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.ResultsUsing 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.ConclusionThe 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
Highlights
GM-CSF is a cytokine which has been shown to actively participate in regulation of Toll-like receptors (TLRs) expression and cytokine production in inflammatory cells
We found that granulocyte-macrophage colony-stimulating factor (GMCSF) were able to upregulate expression of TLR3 and TLR7 on P815 mast cells and provoke IL-13 and IL-6 release from P815 mast cells in the present study
Expression of TLRs in P815 cells In order to ensure if P815 cells are the appropriate cells for the investigation of regulatory effect of GM-CSF on TLR expression, we first examine the expression of TLRs in these cells
Summary
GM-CSF is a cytokine which has been shown to actively participate in regulation of TLR expression and cytokine production in inflammatory cells. As an active proinflammatory cytokine, GM-CSF can be generated by several cell sources including T and B lymphocytes, macrophages, keratinocytes, eosinophils, neutrophils, and mast cells [5]. Recent insight into mast cells has revealed this cell type as key players in the regulation of innate [10] as well as adaptive immunity through TLRs [11,12]. Poly(I:C), R-848, and CpG oligodeoxynucleotide, which are TLR3, TLR7, and TLR9 activators was able to induce proinflammatory cytokines (TNF-alpha and IL-6) and chemokines (RANTES, MIP-1alpha, and MIP-2) release from murine fetal skin-derived cultured mast cells [19]. The mechanisms through which these TLR expressions on mast cells and cytokine release from mast cells were regulated remain poorly understood
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