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Rodrigues, Tamara S; de Sá, Keyla S G; Ishimoto, Adriene Y; Becerra, Amanda; Oliveira, Samuel; Almeida, Leticia; Gonçalves, Augusto V; Perucello, Debora B; Andrade, Warrison A; Castro, Ricardo; Veras, Flavio P; Toller-Kawahisa, Juliana E; Nascimento, Daniele C; de Lima, Mikhael H F; Silva, Camila M S; Caetite, Diego B; Martins, Ronaldo B; Castro, Italo A; Pontelli, Marjorie C; de Barros, Fabio C; do Amaral, Natália B; Giannini, Marcela C; Bonjorno, Letícia P; Lopes, Maria Isabel F; Santana, Rodrigo C; Vilar, Fernando C; Auxiliadora-Martins, Maria; Luppino-Assad, Rodrigo; de Almeida, Sergio C L; de Oliveira, Fabiola R; Batah, Sabrina S; Siyuan, Li; Benatti, Maira N; Cunha, Thiago M; Alves-Filho, José C; Cunha, Fernando Q; Cunha, Larissa D; Frantz, Fabiani G; Kohlsdorf, Tiana; Fabro, Alexandre T; Arruda, Eurico; de Oliveira, Renê D R; Louzada-Junior, Paulo; Zamboni, Dario S
The Journal of experimental medicine, 03/2021, Letnik: 218, Številka: 3Journal Article
Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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