Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo

Abstract

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.

Increased Neuromedin B is Associated with a Favorable Prognosis in Glioblastoma

“…Many reports about the possible role of NMB in tumor cell infiltration have emerged in recent years. Yang reported that NMB and NMBR may be involved in the spontaneous actin polarization of transformed CD8 T cells [22]. However, the correlation analysis of NMB expression and TILs has not been reported in GBM patients.…”

“…The NMBR antagonist PD168368 inhibited the growth of MDA-MB-231 breast cancer cells by inducing cell cycle arrest and apoptosis [21]. Yang reported that BIM-23127, an NMBR antagonist, could potentially inhibit cellular proliferation [22] and induce the death of the medulloblastoma cell line DAOY [23].…”

Identification of Sex-Specific Genetic Polymorphisms Associated with Asthma in Middle-Aged and Older Canadian Adults: An Analysis of CLSA Data

“… 62 Several studies have shown that NMBR plays an innate immune defense role against respiratory viral infection by enhancing IFN-alpha and reducing the expression of IL-6. 63 Females have been shown to have greater Type I IFN responses and are less susceptible to viral infections than males. 64 We reasonably infer that any abnormality or polymorphic alterations in the NMBR gene may have a higher impact on males.…”

Alterations of Pleiotropic Neuropeptide-Receptor gene couples in Cetacea

“…Neuropeptide S ( NPS ) and its receptor ( NPSR1 ) are central to sleep regulation and are linked to the control of feeding behaviour [24, 25, 26]. Neuromedin B Receptor ( NMBR ) has been linked with both hormonal regulation and immunity control [27, 28]. Somatostatin Receptor 4 ( SSTR4 ) plays a role in hormonal regulation and in stress responses [29].…”