Li Chang-Hong, Lu Xin-Jiang, Li Ming-Yun, Chen Jiong
Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo 315211, China.
Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo 315211, China; Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, Ningbo University, Ningbo 315211, China.
Fish Shellfish Immunol. 2015 Dec;47(2):878-85. doi: 10.1016/j.fsi.2015.10.031. Epub 2015 Oct 23.
Cathelicidins (CATHs) are a family of endogenous antimicrobial peptides that are capable of both direct bacteria-killing and immunomodulatory effects. P2X7 receptor (P2X7R) is a mediator of CATH in mammalian immune cells. Here, we studied the function and regulation of CATH in head kidney-derived monocytes/macrophages (MO/MФ) from ayu, Plecoglossus altivelis. We investigated the chemotaxis of MO/MФ in response to ayu CATH (PaCATH), and found that PaCATH had a dose-dependent effect on MO/MФ chemotaxis with the optimal concentration of 10.0 μg/ml. The qPCR and Western blot analysis revealed that PaCATH inhibited the expression of ayu P2X7R (PaP2X7R) at both mRNA and protein levels. Knockdown of the PaP2X7R expression in ayu MO/MФ by RNA interference not only significantly inhibited the chemotactic effect of PaCATH on MO/MФ, but also obviously reduced the effect of PaCATH on the phagocytosis, bacteria-killing, respiratory burst, and cytokine expression of ayu MO/MФ. Our study revealed that the immunomodulatory effect of fish CATH is mediated by P2X7R.
杀菌肽（CATHs）是一类内源性抗菌肽，具有直接杀灭细菌和免疫调节作用。P2X7受体（P2X7R）是CATH在哺乳动物免疫细胞中的介质。在此，我们研究了来自香鱼（Plecoglossus altivelis）头肾来源的单核细胞/巨噬细胞（MO/MФ）中CATH的功能和调控。我们研究了MO/MФ对香鱼CATH（PaCATH）的趋化性，发现PaCATH对MO/MФ趋化性具有剂量依赖性效应，最佳浓度为10.0μg/ml。qPCR和蛋白质印迹分析显示，PaCATH在mRNA和蛋白质水平上均抑制香鱼P2X7R（PaP2X7R）的表达。通过RNA干扰敲低香鱼MO/MФ中PaP2X7R的表达，不仅显著抑制了PaCATH对MO/MФ的趋化作用，还明显降低了PaCATH对香鱼MO/MФ的吞噬作用、细菌杀伤作用、呼吸爆发和细胞因子表达的影响。我们的研究表明，鱼类CATH的免疫调节作用是由P2X7R介导的。
