The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Experimental Manipulation
2.3. Western Blotting Analysis
2.4. Meso Scale Analysis of Cytokines
2.5. Statistical Analysis
3. Results
3.1. Expression of SARS-CoV-2 Receptor ACE2 in A549, A549+, and Caco-2 Cell Lines
3.2. The SARS-CoV-2 S1 Spike Protein Stimulates Production of the Key COVID-19 Inflammatory Cytokine IL-1β in Human A549+ Lung Cells That Is Blocked with the MEK1/2 MAPK ERK1/2 Inhibitor
3.3. The SARS-CoV-2 S1 Spike Protein Activates the MAPK-ERK1/2 and the NF-kB p65 Signaling Pathways in Human A549+ Lung Cells
3.4. The SARS-CoV-2 S1 Spike Protein Stimulates Inflammatory Cytokines IL-6 and IL-8 Production in Caco-2 Human Intestinal Epithelial Cells
3.5. The SARS-CoV-2 S1 Spike Protein Does Not Stimulate MAPK p-ERK1/2 or NF-kB p-p65 Signaling Pathways in Human Caco-2 Intestinal Epithelial Cells
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Forsyth, C.B.; Zhang, L.; Bhushan, A.; Swanson, B.; Zhang, L.; Mamede, J.I.; Voigt, R.M.; Shaikh, M.; Engen, P.A.; Keshavarzian, A. The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells. Microorganisms 2022, 10, 1996. https://doi.org/10.3390/microorganisms10101996
Forsyth CB, Zhang L, Bhushan A, Swanson B, Zhang L, Mamede JI, Voigt RM, Shaikh M, Engen PA, Keshavarzian A. The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells. Microorganisms. 2022; 10(10):1996. https://doi.org/10.3390/microorganisms10101996
Chicago/Turabian StyleForsyth, Christopher B., Lijuan Zhang, Abhinav Bhushan, Barbara Swanson, Li Zhang, João I. Mamede, Robin M. Voigt, Maliha Shaikh, Phillip A. Engen, and Ali Keshavarzian. 2022. "The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells" Microorganisms 10, no. 10: 1996. https://doi.org/10.3390/microorganisms10101996