The University of Toledo Translation Journal of Medical Sciences 
Cardiology Abstract, Department of Medicine Research Symposium UTJMS 2023 May 05; 11(1):e1-e2 

Aerosolized Harmful Algal Bloom Toxin Microcystin-LR 
Induces Inflammatory Signaling in Human Airway 
Epithelial Cells 

Joshua D. Breidenbach, MS1*, Benjamin W. French1, Tamiya T. Gordon1, Andrew L. 
Kleinhenz1, Apurva Lad, MS1, Robin C. Su, PhD1, James C. Willey, MD2, Jeffrey R. 
Hammersley, MD2, R. Mark Wooten, PhD3, Erin L. Crawford, MS1, Nikolai N. 
Modyanov, PhD4, Deepak Malhotra, MD, PhD5, Justin G. Teeguarden, PhD1, Steven 
T. Haller, PhD1, David J. Kennedy, PhD1

1Division of Cardiology, Department of Medicine, The University of Toledo, Toledo, 
OH 43614 
2Division of Pulmonology and Critical Care Medicine, Department of Medicine, The 
University of Toledo, Toledo, OH 43614 
3Division of Infectious Diseases, Department of Medicine, The University of Toledo, 
Toledo, OH 43614 
4Department of Physiology and Pharmacology, The University of Toledo, Toledo, 
OH 43614 
5Division of Nephrology, Department of Medicine, The University of Toledo, 
Toledo, OH 43614 

*Corresponding author: Joshua.breidenbach@rockets.utoledo.edu

Published: 05 May 2023 

Introduction: Harmful algal blooms plague bodies of freshwater globally. These blooms are often 
composed of outgrowths of cyanobacteria capable of producing the heptapeptide Microcystin-LR (MC-
LR) which is a well-known hepatotoxin. Recently, MC-LR has been detected in aerosols generated from 
lake water. However, the risk for human health effects due to MC-LR inhalation exposure have not been 
extensively investigated. 

Methods: In this study, we exposed a fully differentiated 3D human airway epithelium derived from 14 
healthy donors to MC-LR-containing aerosol for 3 minutes per day for 3 days. Concentrations of MC-
LR ranged from 100 pM to 1 µM.   

Results: Although there were little to no detrimental alterations in measures of the airway epithelial 
function (i.e. cell survival, tissue integrity, mucociliary clearance, or cilia beating frequency), a distinct 
shift in the transcriptional activity was found. Genes related to inflammation were found to be 
upregulated such as C-C motif chemokine 5 (CCL5; log2FC = 0.56 , p = 0.02) and C-C chemokine 
receptor type 7 (CCR7; log2FC = 0.83, p = 0.03). Functionally, conditioned media from MC-LR 
exposed airway epithelium was also found to have significant chemo-attractive properties for primary 

https://dx.doi.org/10.46570/utjms.vol11-2023-640 

https://dx.doi.org/10.46570/utjms.vol11-2023-640
mailto:Joshua.breidenbach@rockets.utoledo.edu


https://dx.doi.org/10.46570/utjms.vol11-2023-640 UTJMS 11(1):e1-e2 

https://dx.doi.org/10.46570/utjms.vol11-2023-640 2 ©2023 UTJMS 

human neutrophils. Additionally, increases were found in the concentration of secreted chemokine 
proteins in the conditioned media such as CCL1 (log2FC = 5.07 , p = 0.0001) and CCL5 (log2FC =  
1.02, p = 0.046).    

Conclusion: These results suggest that MC-LR exposure to the human airway epithelium is capable of 
inducing an inflammatory response that may potentiate acute or chronic disease. 

https://dx.doi.org/10.46570/utjms.vol11-2023-640
https://dx.doi.org/10.46570/utjms.vol11-2023-640