Modulation Of Mast Cell Protease Activated Receptor Expression And Cytokines Release By IL-6

Objective: We targeted mast cell PARs expression, IL-4 and IL-13 release as well as the potential signal transduction pathways of IL-6 induced IL-4 and IL-13 release from mast cell P815 to examine the mechanism of IL-6 in alergy and inflammation diseases.Methods: After being challenged, some of P815 cells were treated and analyzed by flowcytometry to detect expression of PARs at protein level, some of cells were treated and analyzed by Q-RT-PCR to detect expression of PARs at mRNA level, and other cells were treated and analyzed by cellular activation of signaling ELISA to detect phosphorylation of Akt,ERK, p38 and STAT3, and the supernatant were analysed by ELISA to detect the release of IL-4,IL-13.Results: The results showed that IL-6 up-regulated PAR-1,PAR-3 and PAR-4 mRNA expression;IL-6 induced IL-4 and IL-13 release from P815 cells following incubation and down-regulated mast cell PAR-1, PAR-3 and PAR-4 expression at protein level. PD98059, U0126 and LY294002 abolished IL-6 induced IL-4 release; LY294002 and U0126 inhibited IL-6 induced IL-13 production; Meanwhile,PD98059, U0126 and LY294002 blocked phosphorylation of ERK and Akt.Conclusion: IL-6 can modulate mast cell PARs expression and IL-4,IL-13 release and may contibute to allergic and inflammation processes by this way. It is most likely through activation of Akt and ERK signaling pathways that IL-6 induced IL-4 and IL-13 release from P815 cells.