Vitamin D regulates COVID-19 associated severity by suppressing the NLRP3 inflammasome pathway.

Autor: Khalil B; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates., Sharif-Askari NS; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates., Hafezi S; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates., Sharif-Askari FS; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates., Al Anouti F; College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates.; ASPIRE Precision Medicine Research Institute, Abu Dhabi, United Arab Emirates., Hamid Q; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada., Halwani R; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Prince Abdullah Ben Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 May 15; Vol. 19 (5), pp. e0302818. Date of Electronic Publication: 2024 May 15 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0302818
Abstrakt: Background: The role of vitamin D3 (VitD3) in modulating innate and adaptive immunity has been reported in different disease contexts. Since the start of the coronavirus disease-2019 (COVID-19) pandemic, the role of VitD3 has been highlighted in many correlational and observational studies. However, the exact mechanisms of action are not well identified. One of the mechanisms via which VitD3 modulates innate immunity is by regulating the NLRP3-inflammasome pathway, being a main underlying cause of SARS-CoV-2-induced hyperinflammation.
Aims and Main Methods: Blood specimens of severe COVID-19 patients with or without VitD3 treatment were collected during their stay in the intensive care unit and patients were followed up for 29 days. qPCR, western blot, and ELISA were done to investigate the mechanism of action of VitD3 on the NLRP3 inflammasome activation.
Key Findings: We here report the ability of VitD3 to downregulate the NLRP3-inflammsome pathway in severe COVID-19 patients. Lower inflammasome pathway activation was observed with significantly lower gene and protein expression of NLRP3, cleaved caspase-1, ASC and IL-1β among severe COVID-19 patients treated with VitD3. The reduction of the inflammasome pathway was associated with a reduction in disease severity markers and enhancement of type I IFN pathway.
Significance: Our data reveals an important anti-inflammatory effect of VitD3 during SARS-CoV-2 infection. Further investigations are warranted to better characterize the ability of VitD3 to control disease pathogenesis and prevent progression to severe states. This will allow for a more efficient use of a low cost and accessible treatment like VitD3.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Khalil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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