NLRP3 Inflammasome Involvement in Heart, Liver, and Lung Diseases—A Lesson from Cytokine Storm Syndrome

Abstract

Inflammation and inflammasomes have been proposed as important regulators of the host–microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1β and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases. It is highly expressed in leukocytes and up-regulated in sentinel cells upon inflammatory stimuli. NLRP3 expression has also been reported in B and T lymphocytes, in epithelial cells of oral and genital mucosa, in specific parenchymal cells as cardiomyocytes, and keratinocytes, and chondrocytes. It is well known that a dysregulated activation of the inflammasome is involved in the pathogenesis of different disorders that share the common red line of inflammation in their pathogenetic fingerprint. Here, we review the potential roles of the NLRP3 inflammasome in cardiovascular events, liver damage, pulmonary diseases, and in that wide range of systemic inflammatory syndromes named as a cytokine storm.

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“…It represents the advanced stage of various CVD, including myocarditis, MI, cardiomyopathy, hypertension, atrial fibrillation, valvular heart disease, alcohol abuse, and infection (Bracey et al, 2013). Recent studies on calcineurin transgene mice have shown elevated mRNA of NLRP3 and enhanced cleavage of caspase-1 along with cardiac hypertrophy and ventricular dilatation (Bracey et al, 2013;Napodano et al, 2023). Genetic ablation of NLRP3 or administration of IL-1 receptor antagonist has been found to attenuate cardiac inflammation and systolic dysfunction (Bracey et al, 2013;Zhang et al, 2014;Napodano et al, 2023).…”

“…Recent studies on calcineurin transgene mice have shown elevated mRNA of NLRP3 and enhanced cleavage of caspase-1 along with cardiac hypertrophy and ventricular dilatation (Bracey et al, 2013;Napodano et al, 2023). Genetic ablation of NLRP3 or administration of IL-1 receptor antagonist has been found to attenuate cardiac inflammation and systolic dysfunction (Bracey et al, 2013;Zhang et al, 2014;Napodano et al, 2023). Additionally, activation of NLRP3 inflammasome has been observed in LPSstimulated cardiac fibroblasts and myofibroblasts, suggesting that its potential contribution to myocardial dysfunction through NLRP3 inflammasome or pyroptosis (Zhang et al, 2014;Boza et al, 2016).…”