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Maltose binding protein enhances interleukin-23 production by dendritic cells through ERK signaling pathway

Yaping Ye  Xuan Zhou  Fangqi Hua  Siting Zheng  Luyan Zheng  Yun Zhou  Yujie He  Baoming Wang  Dayong Zhang  Jianping Pan  
【摘要】:Objective:It was found that maltose binding protein(MBP) has extensive immunologically regulatory effects,including activation of NK cells,macrophages and Th1 cells.In fact,it was also reported that CD4+ T cells from spleens of mice intranasally immunized with fusion protein of MBP and rotavirus VP6 produced significantly increased concentrations of IL-17,implying that MBP might facilitate Th17 differentiation.Furthermore,our previous study showed that MBP promoted IL-23,but not IL-1β,IL-6 and IL-12 production by dendritic cells(DC).Because IL-23 plays a very important role in the differentiation and maturation of Th17 cells,the aim of the present study is to explore the influence of MBP on IL-23 production and its molecular mechanism in DC,so as to provide evidence for further examination of the influence of MBP on Th17 differentiation and maturation.Materials and methods:1×106 cells of DC2.4 were incubated in 24-well plate with different concentrations of MBP(0,1,5 μg/ml).Supernatants were harvested for measurement of IL-23.Proteins were extracted from the cells and used for western blot analyses of signal transduction pathway.To confirm the role of ERK signaling pathway in MBP induced IL-23 production by DC,ERK inhibitor PD-98059(1μM)was used.Results:MBP dose-dependently enhanced the production of IL-23 by DC2.4.Concentrations of IL-23 in the control group,1 μg/ml MBP group and 5 fig/ml MBP group were 2.3±2.08 pg/ml,26.4±2.08 pg/ml and 31.4±2.12 pg/ml,respectively.Western blot analyses showed that levels of AKT,p-AKT(Ser-473),p-p38(Thr-180/Tyr-182) remained unchanged,but levels of p-ERK(Thr-202/Tyr-204)increased significantly after treatment of MBP,suggesting that ERK signaling pathway might play a key role in the MBP induced production of IL-23 by DC.When the ERK inhibitor PD-98059(1μM) was employed to block the ERK signaling pathway,the enhancing effect of MBP on IL-23 production by DC was profoundly abrogated.Conclusion:MBP promote DC to secrete EL-23 mainly through ERK signaling pathway.

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