Mesenchymal stromal cell treatment in Coxsackievirus B3-infected mice reduced left ventricular NLRP3 mRNA expression by 10.6-fold and suppressed inflammasome activation.
Does mesenchymal stromal cell treatment inhibit NLRP3 inflammasome activation in a model of Coxsackievirus B3-induced inflammatory cardiomyopathy?
Mesenchymal stromal cell treatment inhibits NLRP3 inflammasome activation in CVB3-induced myocarditis, suggesting a potential therapeutic strategy for limiting adverse consequences of inflammatory cardiomyopathy.
Effect estimate: 10.6-fold reduction
p-value: p=<0.005
Inflammation in myocarditis induces cardiac injury and triggers disease progression to heart failure. NLRP3 inflammasome activation is a newly identified amplifying step in the pathogenesis of myocarditis. We previously have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA expression in CVB3-infected mice. ASC protein expression, essential for NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated in MSC-treated mice. Concomitantly, CVB3 infection in vitro induced NOD2 expression, NLRP3 inflammasome activation and IL-1β secretion in HL-1 cells, which was abolished after MSC supplementation. The inhibitory effect of MSC on NLRP3 inflammasome activity in HL-1 cells was partly mediated via secretion of the anti-oxidative protein stanniocalcin-1. Furthermore, MSC application in CVB3-infected mice reduced the percentage of NOD2-, ASC-, p10- and/or IL-1β-positive splenic macrophages, natural killer cells, and dendritic cells. The suppressive effect of MSC on inflammasome activation was associated with normalized expression of prominent regulators of myocardial contractility and fibrosis to levels comparable to control mice. In conclusion, MSC treatment in myocarditis could be a promising strategy limiting the adverse consequences of cardiac and systemic NLRP3 inflammasome activation.
Miteva et al. (Tue,) conducted a other in Coxsackievirus B3-induced inflammatory cardiomyopathy. Mesenchymal stromal cells (MSC) vs. PBS was evaluated on Left ventricular NLRP3 mRNA expression (10.6-fold reduction, p=<0.005). Mesenchymal stromal cell treatment in Coxsackievirus B3-infected mice reduced left ventricular NLRP3 mRNA expression by 10.6-fold and suppressed inflammasome activation.