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Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo.
Veterinary Research ( IF 3.7 ) Pub Date : 2019-10-10 , DOI: 10.1186/s13567-019-0695-2
Guihong Yang , Huipeng Huang , Mengyao Tang , Zifeng Cai , Cuiqin Huang , Baomin Qi , Ji-Long Chen

The peptide neuromedin B (NMB) and its receptor (NMBR) represent a system (NMB/NMBR) of neuromodulation. Here, it was demonstrated that the expression of NMBR in cells or murine lung tissues was clearly upregulated in response to H1N1/PR8 influenza A virus infection. Furthermore, the in vitro and in vivo activities of NMB/NMBR during PR8 infection were investigated. It was observed that A549 cells lacking endogenous NMBR were more susceptible to virus infection than control cells, as evidenced by the increased virus production in the cells. Interestingly, a significant decrease in IFN-α and increased IL-6 expression were observed in these cells. The role of this system in innate immunity against PR8 infection was probed by treating mice with NMB. The NMB-treated mice were less susceptible to virus challenge, as evidenced by increased survival, increased body weight, and decreased viral NP expression compared with the control animals. Additionally, the results showed that exogenous NMB not only enhanced IFN-α expression but also appeared to inhibit the expression of NP and IL-6 in PR8-infected cells and animals. As expected, opposing effects were observed in the NMBR antagonist-treated cells and mice, which further confirmed the effects of NMB. Together, these data suggest that NMB/NMBR may be an important component of the host defence against influenza A virus infection. Thus, these proteins may serve as promising candidates for the development of novel antiviral drugs.

中文翻译:

神经调节素B及其受体在体内和体外针对甲型流感病毒感染的先天免疫应答中的作用。

肽神经调节素B(NMB)及其受体(NMBR)代表神经调节系统(NMB / NMBR)。在这里,证明了响应于H1N1 / PR8 A型流感病毒感染,NMBR在细胞或鼠肺组织中的表达明显上调。此外,还研究了PR8感染期间NMB / NMBR的体外和体内活性。观察到缺乏内源性NMBR的A549细胞比对照细胞更容易受到病毒感染,这由细胞中病毒产生的增加所证明。有趣的是,在这些细胞中观察到IFN-α的显着降低和IL-6表达的升高。通过用NMB处理小鼠,探索了该系统在抵抗PR8感染的先天免疫中的作用。经NMB处理的小鼠存活率降低证明了其对病毒攻击的敏感性降低,与对照动物相比,体重增加,而病毒NP表达降低。另外,结果表明,外源NMB不仅增强了IFN-α的表达,而且似乎抑制了PR8感染的细胞和动物中NP和IL-6的表达。如所预期的,在NMBR拮抗剂处理的细胞和小鼠中观察到相反的作用,这进一步证实了NMB的作用。总之,这些数据表明,NMB / NMBR可能是宿主抵抗甲型流感病毒感染的重要组成部分。因此,这些蛋白质可以作为开发新型抗病毒药物的有希望的候选物。结果表明,外源NMB不仅增强了IFN-α的表达,而且似乎抑制了PR8感染的细胞和动物中NP和IL-6的表达。如所预期的,在NMBR拮抗剂处理的细胞和小鼠中观察到相反的作用,这进一步证实了NMB的作用。总之,这些数据表明,NMB / NMBR可能是宿主抵抗甲型流感病毒感染的重要组成部分。因此,这些蛋白质可以作为开发新型抗病毒药物的有希望的候选物。结果表明,外源性NMB不仅增强了IFN-α的表达,而且似乎抑制了PR8感染的细胞和动物中NP和IL-6的表达。如所预期的,在NMBR拮抗剂处理的细胞和小鼠中观察到相反的作用,这进一步证实了NMB的作用。总之,这些数据表明,NMB / NMBR可能是宿主抵抗甲型流感病毒感染的重要组成部分。因此,这些蛋白质可以作为开发新型抗病毒药物的有希望的候选物。
更新日期:2019-10-10
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