Organic Dust Exposure Enhances SARS-CoV-2 Entry in a PKCα- and ADAM-17-Dependent Manner
Abstract
:1. Introduction
2. Materials and Methods
2.1. SARS-CoV-2 Pseudovirus
2.2. Mice Experiments
2.3. Mouse Lung ACE2 Quantitation
2.4. RNA Extraction and Quantitative Polymerase Chain Reaction (qPCR)
2.5. BEAS-2B Cells
2.6. PKCα Activity Assay
2.7. BEAS-2B Cell Treatments and Infection
2.8. ACE2 Expression by Flow Cytometry
2.9. Quantification of BEAS-2B Pseudovirus Infection by Immunofluorescence
2.10. Interleukin-8 (IL-8) ELISA
2.11. Statistical Analysis
3. Results
3.1. ODE Single and Repetitive Exposure Increases Murine Lung Soluble ACE2 Levels Dependent upon ADAM-17 with an Associated Effect on SARS-CoV-2 Pseudovirus Infectivity
3.2. ODE Treatment Increases Human Bronchial Epithelial Cell PKCα Activity
3.3. Inhibition of PKCα and ADAM-17 along with ODE Treatment Synergistically Increases Membrane ACE2 Levels, Enhancing SARS-CoV-2 Pseudovirus Entry in BEAS-2B Cells In Vitro
3.4. SARS-CoV-2 Pseudovirus Infection Reduces IL-8 Secretion in a PKCα-Independent Manner in Low-Dose ODE-Treated BEAS-2B Cells
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Muralidharan, A.; Bauer, C.D.; Nissen, C.G.; Reid, S.P.; Poole, J.A.; Wyatt, T.A. Organic Dust Exposure Enhances SARS-CoV-2 Entry in a PKCα- and ADAM-17-Dependent Manner. Int. J. Transl. Med. 2024, 4, 486-497. https://doi.org/10.3390/ijtm4030032
Muralidharan A, Bauer CD, Nissen CG, Reid SP, Poole JA, Wyatt TA. Organic Dust Exposure Enhances SARS-CoV-2 Entry in a PKCα- and ADAM-17-Dependent Manner. International Journal of Translational Medicine. 2024; 4(3):486-497. https://doi.org/10.3390/ijtm4030032
Chicago/Turabian StyleMuralidharan, Abenaya, Christopher D. Bauer, Claire G. Nissen, St Patrick Reid, Jill A. Poole, and Todd A. Wyatt. 2024. "Organic Dust Exposure Enhances SARS-CoV-2 Entry in a PKCα- and ADAM-17-Dependent Manner" International Journal of Translational Medicine 4, no. 3: 486-497. https://doi.org/10.3390/ijtm4030032