Abstract
Regulation of hyaluronic acid synthesis and breakdown can prevent significant damage of the lung epithelium in response to SARS-CoV-2 infection
Physiology (Bethesda, Md.), Vol.38(S1)
05/01/2023
DOI: 10.1152/physiol.2023.38.s1.5732829
Abstract
COVID-19 remains an ongoing global pandemic causing significant respiratory distress and endothelial dysfunction in individuals susceptible to severe disease. Increased production of hyaluronic acid has been observed in patients with severe COVID-19, however its significance in COVID-19 pathogenesis is currently unknown. Hymecromone is a hyaluronic acid synthase inhibitor FDA approved for use in humans as a choleretic. We hypothesized that excessive production of hyaluronic acid by the airway epithelium, in response to SARS-CoV-2 infection, may increase hyaluronan fragments that augment epithelial dysfunction in COVID-19. We therefore evaluated a hyaluronic acid synthase inhibitor, hymecromone, for its potential to regulate the infection of respiratory epithelia by SARS-CoV-2. Using air-liquid interface models we evaluated the impact of SARS-CoV-2 infection on differentiated primary human airway epithelium in the BSL3 facility. At 100μg/ml hymecromone significantly inhibited the cytopathic effects of SARS-CoV-2 on airway epithelium (p<0.001). After 24 hours, SARS-CoV-2 virus accumulated in the basolateral compartment after apical infection of the airway cultures. Hymecromone also significantly inhibited this basolateral accumulation of viral particles versus untreated controls (p<0.05). Additionally, hymecromone alters the cytokine response to SARS-CoV-2 infection, dose-dependently decreasing apical secretion of cytokines including IL-17A/B/D, IL-21 and IL-5, and dose-dependently increasing the basolateral secretion of IL-17A/D and IL-1RA. All experiments were performed on three independent donor cells with three experimental repeats per condition. In conclusion, our data highlight the importance of the regulation of hyaluronic acid production in the response of the airway epithelium to SARS-CoV-2 infection and indicate hymecromone as a potential therapeutic option. Funding for this study was provided by the Rainwater Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Details
- Title: Subtitle
- Regulation of hyaluronic acid synthesis and breakdown can prevent significant damage of the lung epithelium in response to SARS-CoV-2 infection
- Creators
- Noa Harriott - University of IowaBen Calvert - University of IowaErik Quiroz - University of IowaAmy Ryan - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.38(S1)
- Publisher
- American Physiological Society
- DOI
- 10.1152/physiol.2023.38.s1.5732829
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Language
- English
- Date published
- 05/01/2023
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984532059102771
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