COVID-19 Induces Greater NLRP3 Inflammasome Activation in Obese Patients than Other Chronic Illnesses: A Case-Control Study

被引：0
作者：
D'Amico, Raissa Campos [1 ,2 ]
Nagashima, Seigo [1 ]
Carstens, Lucas Baena [1 ,2 ]
Bertoldi, Karina de Guadalupe [1 ]
Mataruco, Sabrina [2 ]
Honorio D'Agostini, Julio Cesar [3 ]
Hlatchuk, Elisa Carolina [3 ]
da Silva, Sofia Brunoro [2 ]
de Noronha, Lucia [1 ,2 ,3 ]
Baena, Cristina Pellegrino [1 ,2 ]
机构：
[1] Pontificia Univ Catolica Parana, Postgrad Program Hlth Sci PPGCS, BR-80215901 Curitiba, PR, Brazil
[2] Pontificia Univ Catolica Parana, Sch Med, BR-80215901 Curitiba, PR, Brazil
[3] Univ Fed Parana, Sch Med, BR-80060240 Curitiba, PR, Brazil
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2025年 / 26卷 / 04期
关键词：
COVID-19; SARS-CoV-2; inflammasome; pyroptosis; obesity; HYPOXIA; INTERLEUKIN-6; CASPASES; ROLES;
D O I：
10.3390/ijms26041541
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Obesity has been identified as an independent risk factor for severe COVID-19 unfavorable outcomes. Several factors, such as increased ACE2 receptor expression and chronic inflammation, can contribute to this relationship, yet the activation of the NLRP3 inflammasome pathway is also a key element. Our primary goal was to determine whether chronic NLRP3 inflammasome activation in people with obesity is different in critical COVID-19 and in critical chronic conditions. A retrospective analysis was conducted using clinical data and post-mortem lung tissue samples from 14 COVID-19 patients with obesity (group A) and 9 patients with obesity who died from non-COVID-19 causes (group B). Immunohistochemical analysis assessed twelve markers related to the NLRP3 inflammasome pathway. Group A showed a significantly higher expression of ASC (p = 0.0387) and CASP-1 (p = 0.0142). No significant differences were found for IL-8, TNF-alpha, NF-kB, NLRP3, IL-1 beta, and gasdermin-D. Group B had higher levels of IL-6 (p < 0.0001), IL-18 (p = 0.002), CASP-9 (p < 0.0001), and HIF (p = 0.0327). We concluded that COVID-19 activates the NLRP3 inflammasome pathway, possibly leading to pyroptotic cell death mediated by caspase-1. In contrast, people with obesity without COVID-19, despite exhibiting some markers of the NLRP3 inflammasome, are more likely to experience necroptosis mediated by caspase-9.
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页数：14
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