Abstract
Influenza remains one of the major epidemic diseases worldwide. Acute lung injury mainly caused by excessive pro-inflammatory host immune responses leads to high mortality rates in severe influenza patients. Galectin-1, an animal lectin ubiquitously expressed in mammalian tissues, is reported to play important roles in viral diseases. Here, we established murine and A549 cell models to explore the potential roles of galectin-1 treatment in H1N1pdm09-induced acute lung injury. We found that galectin-1 protein level was elevated in A549 cell culture supernatants and mouse BALF after H1N1pdm09 challenge. In vivo experiments showed recombinant galectin-1 treatment reduced wet/dry weight ratio, inflammatory cell infiltration in mouse lungs and mediated the expression of cytokines and chemokines including IL-1β, IL-6, IL-10, IL-12(p40), IL-12(p70), G-CSF, MCP-1, MIP-1α and RANTES in serum and BALF of infected mice. Reduced apoptosis and viral titers in mouse lungs were also found after galectin-1 treatment. As expected, galectin-1 treated mice performed reduced body weight loss and enhanced survival rate against H1N1pdm09 challenge. In addition, in vitro experiments showed that viral titers decreased in a dose-dependent manner and cell apoptosis in A549 cells reduced after recombinant galectin-1 treatment. Taken together, our findings indicate a potentially positive effect of Gal-1 treatment on ameliorating the progress of H1N1pdm09-induced acute lung injury and recombinant galectin-1 might serve as a new agent in treating influenza.
Highlights
Influenza is a major public health concern, yearly causing about 250,000–500,000 deaths worldwide, and has not been restrained so far (Thompson et al, 2018)
Results indicated the presence of progressively increased viral HA, NP, M1 and NS1 copies in A549 cells infected by H1N1pam09 at indicated time points (Figures 1A–D)
Lungs from uninfected mice had no apparent histopathological lesions (Figure 1I). These results suggested that H1N1pdm09 could replicate effectively in A549 cells and mouse lungs and could lead to typical acute lung injury in mice, which showed a success in the establishment of cell and mouse infection model, laying a foundation for the following experiments
Summary
Influenza is a major public health concern, yearly causing about 250,000–500,000 deaths worldwide, and has not been restrained so far (Thompson et al, 2018). Inflammatory mediators recruit immune cells to the infected site for viral clearance; on the other hand, excessive activation of immune response aggravates lung tissue injury, which can accelerate the progress and worsen outcomes of the disease, and be considered as the primary cause of ALI (Newton et al, 2016). Such therapeutic strategies aiming to reduce an unbalanced, overshooting inflammation, which have good effects on IAV-induced ALI, may be an alternative approach for the treatment of IAV infection (Herold et al, 2015)
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