| Autor: |
Magdalena Ambrożek-Latecka, Piotr Kozlowski, Grażyna Hoser, Magdalena Bandyszewska, Karolina Hanusek, Dominika Nowis, Jakub Gołąb, Małgorzata Grzanka, Agnieszka Piekiełko-Witkowska, Luise Schulz, Franziska Hornung, Stefanie Deinhardt-Emmer, Ewa Kozlowska, Tomasz Skirecki |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cell Death Discovery, Vol 10, Iss 1, Pp 1-11 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2058-7716 |
| DOI: |
10.1038/s41420-024-01966-9 |
| Popis: |
Abstract Inflammasome assembly is a potent mechanism responsible for the host protection against pathogens, including viruses. When compromised, it can allow viral replication, while when disrupted, it can perpetuate pathological responses by IL-1 signaling and pyroptotic cell death. SARS-CoV-2 infection was shown to activate inflammasome in the lungs of COVID-19 patients, however, potential mechanisms responsible for this response are not fully elucidated. In this study, we investigated the effects of ORF3a, E and M SARS-CoV-2 viroporins in the inflammasome activation in major populations of alveolar sentinel cells: macrophages, epithelial and endothelial cells. We demonstrated that each viroporin is capable of activation of the inflammasome in macrophages to trigger pyroptosis-like cell death and IL-1α release from epithelial and endothelial cells. Small molecule NLRP3 inflammasome inhibitors reduced IL-1 release but weakly affected the pyroptosis. Importantly, we discovered that while SARS-CoV-2 could not infect the pulmonary microvascular endothelial cells it induced IL-1α and IL-33 release. Together, these findings highlight the essential role of macrophages as the major inflammasome-activating cell population in the lungs and point to endothelial cell expressed IL-1α as a potential novel component driving the pulmonary immunothromobosis in COVID-19. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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