Aerosolized microcystin-LR exacerbates chemokines and other inflammatory mediators of asthma in asthmatic primary human airway epithelium
Start Date
23-5-2022 5:45 PM
End Date
23-5-2022 7:00 PM
Abstract
Microcystin-LR, one of the most abundant and toxic HAB-derived cyanotoxins, has recently been detected in aerosols from HAB water. We previously reported that aerosol MC-LR exposure has a pro-inflammatory influence on the airways. Asthma, which is an extremely prevalent airway disease afflicting approximately 8% of the U.S. population, is largely driven by inflammation. However, the impact of MC-LR aerosol exposure on this at-risk population is unknown. In this study, a 3D primary human airway epithelium model was utilized, in which cells were isolated from healthy and asthmatic donors. An environmentally relevant concentration of MC-LR (1 μM) was aerosolized and delivered to the cell surface, before the cells were harvested for transcriptome analysis. Strikingly, 10% of the genes upregulated (log2FC > 0.25) by asthma alone, were further upregulated by MC-LR exposure including inflammation mediators, such as CXCL11 (log2FC = 0.63); and TLR4 (log2FC = 0.31). These genes had significant associations with pathways, such as “immune cytokine binding” (FDR = 0.015). This study showed that aerosolized MC-LR amplifies the transcriptional differences between asthmatic and healthy donor airway epithelial cells, leading to the exacerbation of inflammatory mediators of asthma, such as chemokines, suggesting a potential for MC-LR exposure to worsen asthma severity.
Aerosolized microcystin-LR exacerbates chemokines and other inflammatory mediators of asthma in asthmatic primary human airway epithelium
Microcystin-LR, one of the most abundant and toxic HAB-derived cyanotoxins, has recently been detected in aerosols from HAB water. We previously reported that aerosol MC-LR exposure has a pro-inflammatory influence on the airways. Asthma, which is an extremely prevalent airway disease afflicting approximately 8% of the U.S. population, is largely driven by inflammation. However, the impact of MC-LR aerosol exposure on this at-risk population is unknown. In this study, a 3D primary human airway epithelium model was utilized, in which cells were isolated from healthy and asthmatic donors. An environmentally relevant concentration of MC-LR (1 μM) was aerosolized and delivered to the cell surface, before the cells were harvested for transcriptome analysis. Strikingly, 10% of the genes upregulated (log2FC > 0.25) by asthma alone, were further upregulated by MC-LR exposure including inflammation mediators, such as CXCL11 (log2FC = 0.63); and TLR4 (log2FC = 0.31). These genes had significant associations with pathways, such as “immune cytokine binding” (FDR = 0.015). This study showed that aerosolized MC-LR amplifies the transcriptional differences between asthmatic and healthy donor airway epithelial cells, leading to the exacerbation of inflammatory mediators of asthma, such as chemokines, suggesting a potential for MC-LR exposure to worsen asthma severity.