SynAir-G has continued to investigate how environmental exposures affect the lungs using in vitro research methods, including studies with human nasal epithelial cells. This research aims to better understand how environmental factors induce inflammatory responses and interact with respiratory conditions such as asthma. As environmental exposures rarely act in isolation, understanding the interactions and potential synergies between different exposures and underlying lung conditions is essential for developing more targeted approaches to prevention and care.
From viral triggers of asthma exacerbations…
The Rhinovirus (RV) is one of the most common causes of the common cold, and also a major trigger of asthma exacerbations. However, the timing and progression of the epithelial responses underlying these exacerbations are not yet fully understood.
To investigate this, the SynAir-G WP4 team studied the temporal response to RV infection in primary human nasal epithelial cells (hNECs) obtained from donors with and without asthma. The cells were monitored at multiple time points following infection to understand how their responses developed over time.
The findings showed that the infection persisted for at least 48 hours and triggered a broad range of responses in the epithelial cells, including antiviral, inflammatory, and stress-related pathways. In particular, interferon-associated responses, which support antiviral defense through signalling by interferon (IFN) proteins, showed clear time-dependent regulation. IFN-λ-related gene expression increased early after infection, while downstream interferon-stimulated genes remained elevated at later time points. Other inflammatory mediators also displayed distinct patterns over time.
These findings show that the epithelial response to RV infection is highly dynamic and evolves throughout the course of infection, rather than occurring as one uniform event, highlighting the importance of studying RV infection at multiple time points.
The research also measured oxidative stress using the DCFDA assay, which assesses intracellular reactive oxygen species (ROS). The results showed increased ROS levels in the epithelial cells following RV infection. This is particularly relevant because oxidative stress can influence inflammatory signalling, epithelial barrier integrity, and antiviral defense.
Taken together, these findings highlight how different biological responses, including antiviral defense, inflammation, and oxidative stress, can occur simultaneously and interact with one another. A better understanding of these processes may help clarify how viral respiratory infections contribute to inflammation and asthma exacerbations, supporting the development of more targeted approaches to protecting people living with asthma and other airway diseases.
… to the impact of air pollution
In a related line of research, the SynAir-G team exposed nasal epithelial cells to another environmental trigger: particulate matter (PM). This air pollutant primarily originates from outdoor sources such as traffic, industry, and agriculture, but can also enter buildings and contribute significantly to indoor air pollution. Both healthy and asthmatic nasal epithelial cells were exposed.
The team conducted a multiplex ELISA analysis of the epithelial cell culture supernatants. This technique measures the proteins released by the cells into the surrounding liquid and helps understand the reaction of the epithelial cells in response to a stimulus like PM.
The analysis revealed a significant increase in the release of cytokine proteins, which are involved in immune regulation and inflammatory signalling. Notably, epithelial cells from donors with asthma secreted significantly higher levels of pro-inflammatory cytokines than cells from healthy control donors. These findings suggest that epithelial cells from people with asthma may display an exaggerated inflammatory response to PM exposure. This provides further insight into how air pollution could contribute to airway inflammation and potentially worsen respiratory symptoms in people living with asthma.
Next Steps
This in-vitro research further highlights the importance of investigating how environmental exposures, including viral infections and air pollution, affect the respiratory system. These exposures can trigger multiple interconnected responses in airway epithelial cells, which may differ in people living with respiratory diseases and potentially contribute to disease worsening. Understanding these mechanisms is particularly important for protecting vulnerable populations.
The research reinforces the importance of clean air, particularly for people living with asthma and allergic respiratory diseases. By continuing to investigate these mechanisms, SynAir-G aims to contribute to the development of targeted interventions and innovative solutions, while supporting greater awareness and evidence-based policy action to protect respiratory health.
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