Abstract
Influenza virus has a significant impact on the respiratory system. The mechanism of how influenza virus impairs the fluid transport in airway is not fully understood. We examined its effects on epithelial sodium channels (ENaC), which are very important for water and salt transport in the respiratory system. We focused on the impacts of influenza virus on ENaC activity in mouse tracheal epithelial cells (MTECs) and applied Ussing chamber apparatus for recording the short-circuit currents in primary cultured MTECs. Expressions of α and γ-ENaC were measured at the protein and mRNA levels by western blot and quantitative real-time polymerase chain reaction, respectively. Roles of the with-no-lysine-kinase-4 (WNK4) pathway were considered in participating influenza virus-involved ENaC regulation by using siRNA to knockdown WNK4 and the physical properties of airway surface liquid (ASL) were detected by confocal microscopy. Our results showed that influenza virus reduced ENaC activity, and the expressions of α and γ-ENaC were decreased at the protein and mRNA levels, respectively. WNK4 expression increased time-dependently at the protein level after influenza virus infection, while knockdown of WNK4 rescued the impact of influenza virus on ENaC and ASL height increased obviously after MTECs were treated with influenza virus. Taken together, these results suggest that influenza virus causes the changes of biophysical profile in the airway by altering the ENaC activity at least partly via facilitating the expression of WNK4.
Highlights
Influenza is an infectious disease caused by influenza virus
First we testified the effect of influenza virus on the transport of Na+ by measuring amiloride-sensitive short-circuit currents (Isc) (ASI) in Ussing chamber system
The results showed that influenza virus infection reduced Isc, which could be blocked by 100 μM amiloride, a specific epithelial sodium channels (ENaC) inhibitor (Figure 1A)
Summary
Influenza is an infectious disease caused by influenza virus. There are three kinds of influenza viruses, A, B, and C, among which influenza virus A and B regularly infect humans and are responsible for influenza epidemics (Londino et al, 2017). Mouse tracheal epithelial cells (MTECs) are mainly composed of the polarized columnar cells with a brush of cilia on the top (Ibricevic et al, 2006), and the polarized epithelial cells and extracellular fluid constitute the first physical barrier to the respiratory system for harmful substances such as virus and bacteria. ASL at least consists of mucus layer and preciliary liquid layer, the former of which contains highly glycosylated mucins rich in terminal sialic acid, and is thought to be able to trap influenza virus from the environment and eliminate them from respiration system by cilia beating in a mechanical manner (Knowles and Boucher, 2002; Lillehoj and Kim, 2002; Matrosovich and Klenk, 2003; Duez et al, 2009; Barbier et al, 2012). The height of ASL is a common index reflecting the ability of fluid transport under pathological conditions
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