天然辅助细胞通过p38信号通路分泌IL-13

Natural help cells produce IL-13by activating p38 signaling pathway during RSV infection

目的 RSV感染后,天然辅助细胞(Natural helper cells,NHC)通过IL-33/ST2途径产生IL-13,对于IL-33激活的下游信号通路尚不明确。IL-33通过其受体ST2激活NF-κB和MAPK信号通路,进而诱导极化的Th2细胞分泌Th2型细胞因子。本研究旨在通过一系列体内外实验探究NF-κB和MAPK信号通路在天然辅助细胞IL-13分泌机制中的作用。方法在IL-33刺激前用特异性NF-κB和p38抑制剂对NHC进行预处理,实时RT-PCR和流式细胞仪技术分别检测mRNA水平及NF-κB和MAPK磷酸化情况。结果 NHC中p38mRNA和磷酸化水平都显著升高;并且,p38特异性抑制剂显著降低NHC中IL-13分泌量。另一方面,NF-kB mRNA及磷酸化水平升高,但NF-κB的特异性抑制剂并没有显著抑制NHC分泌IL-13。结论 RSV诱导的NHC中IL-13的产生依赖于p38信号通路。

Objective Natural helper cells can produce IL-13 via the IL-33/ST2 pathway during RSV infection,and the downstream signaling pathway for IL-33 activation is unclear.IL-33 activates NF-κB and MAPK signaling pathways through its receptor ST2,which in turn induces the secretion of Th2 type cytokines by polarized Th2 cells.The purpose of this study was to explore the role of NF-κB and MAPK signaling pathways in the secretion of IL-13 in NHC through a series of in vitro and in vivo experiments.Methods NHC were pretreated with specific NF-κB and p38 inhibitors prior to IL-33 stimulation.Real-time RT-PCR and flow cytometry were used to detect mRNA levels and phosphorylations for NF-κB and MAPK,respectively.Results The levels of mRNA and phosphorylation for p38 were significantly elevated in NHC;furthermore,p38-specific inhibitors significantly reduced IL-13 secretion in NHC.On the other hand,the expression of NF-kB mRNA as well as the level of phosphorylated p38 protein were elevated,but specific inhibitors of NF-kB did not significantly inhibit the secretion of IL-13 in NHC.Conclusion RSV-induced IL-13 production in NHC is dependent on the p38 signaling pathway.