Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis

Wang, Yan; Gao, Bo; Xiong, Sidong

doi:10.1152/ajpheart.00441.2014

Cited by 95 publications

(92 citation statements)

References 50 publications

(54 reference statements)

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“…NLRP3 inflammasome activation in CMs has been described during viral myocarditis after coxsackievirus B3 infection (35). Inhibition of inflammasome activation with a pan‐caspase‐1 inhibitor resulted in reduced intensity of myocardial injury in this model along with improved cardiac function.…”

Section: Discussionmentioning

confidence: 99%

Complement‐induced activation of the cardiac NLRP3 inflammasome in sepsis

Kalbitz

Fattahi²,

Grailer³

et al. 2016

FASEB j.

107

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Cardiac dysfunction develops during sepsis in humans and rodents. In the model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we investigated the role of the NLRP3 inflammasome in the heart. Mouse heart homogenates from sham-procedure mice contained high mRNA levels of NLRP3 and IL-1β. Using the inflammasome protocol, exposure of cardiomyocytes (CMs) to LPS followed by ATP or nigericin caused release of mature IL-1β. Immunostaining of left ventricular frozen sections before and 8 h after CLP revealed the presence of NLRP3 and IL-1β proteins in CMs. CLP caused substantial increases in mRNAs for IL-1β and NLRP3 in CMs which are reduced in the absence of either C5aR1 or C5aR2. After CLP, NLRP3 mice showed reduced plasma levels of IL-1β and IL-6. In vitro exposure of wild-type CMs to recombinant C5a (rC5a) caused elevations in both cytosolic and nuclear/mitochondrial reactive oxygen species (ROS), which were C5a-receptor dependent. Use of a selective NOX2 inhibitor prevented increased cytosolic and nuclear/mitochondrial ROS levels and release of IL-1β. Finally, NLRP3 mice had reduced defects in echo/Doppler parameters in heart after CLP. These studies establish that the NLRP3 inflammasome contributes to the cardiomyopathy of polymicrobial sepsis.-Kalbitz, M., Fattahi, F., Grailer, J. J., Jajou, L., Malan, E. A., Zetoune, F. S., Huber-Lang, M., Russell, M. W., Ward, P. A. Complement-induced activation of the cardiac NLRP3 inflammasome in sepsis.

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Section: Discussionmentioning

confidence: 99%

Complement‐induced activation of the cardiac NLRP3 inflammasome in sepsis

Kalbitz

Fattahi²,

Grailer³

et al. 2016

FASEB j.

107

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“…Caspase-1 is the primary activator of the inflammatory cytokines IL-1B and IL-18, and plays a major role in the pathogenesis of viral myocarditis 16,31,32 . A previous study showed that heart tissue from patients with viral myocarditis had increased caspase-1 expression, and the intensity of expression was directly related to the severity of heart failure and lack of functional recovery at 6 months 33 .…”

Section: Discussionmentioning

confidence: 99%

Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

Zamudio

Henderson-Frost

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction: Trypanosoma cruzi (Tc) infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20-30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs) with cardiomyopathy. Methods: We recruited infected (Tc+, n = 149) and uninfected (Tc−, n = 87) participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV) based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive) using logistic regression adjusted for age and sex. Results: The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV) patients compared to those with a normal cardiac status (class I) [odds ratio (OR) = −2.18, p = 0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR = −2.64, p = 0.064). Conclusions: Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.

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“…Furthermore, IL-1β is known to be also involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis [22]. In addition to its pathophysiologic role in host protection, IL-1β pro- motes the progression of a number of autoimmune diseases: autoimmune thyroid diseases [23], diabetes mellitus [24], multiple sclerosis [25], and myocarditis [26]. IL-1β is also associated with febrile seizures [27], epilepsy [28], and gout [29].…”

Section: Discussionmentioning

confidence: 99%

Production of recombinant human interleukin-38 and its inhibitory effect on the expression of proinflammatory cytokines in THP-1 cells

Yuan

Pan

et al. 2016

Mol Biol

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Interleukin (IL)-38 is the latest member of the IL-1 cytokine family. However, as a result of lacking efficient method to generate relatively large quantity of IL-38, its precise functions are poorly understood. In the present study, the cloning, expression, purification, and activity analysis of recombinant human IL-38 was described. Human IL-38 cDNA was cloned into the prokaryotic expression vector pET-44. The recombinant IL-38 containing a C-hexahistidine tag was expressed in Escherichia coli BL21 (DE3) which induced by isopropyl-β-D-thiogalactoside. The expressed fusion protein was purified by Ni-NTA affinity chromatography. IL-38 protein was largely found in the soluble fraction. The purified IL-38 appeared a single band on SDS-PAGE, the yield of IL-38 was 4 mg from 1 L of bacterial culture, and the purity was more than 98% with low endotoxin level (<0.1 EU/μg). Western blotting confirmed the identity of the purified protein. Activity analysis showed that IL-38 can inhibit effectively the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-1β, IL-17, and monocyte chemoattractant protein-1 in lipopolysaccharide-activated THP-1 cells. The production and characterization of biologically active IL-38 will be beneficial for its potential role in clinical applications.

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Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis

Cited by 95 publications

References 50 publications

Complement‐induced activation of the cardiac NLRP3 inflammasome in sepsis

Complement‐induced activation of the cardiac NLRP3 inflammasome in sepsis

Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

Production of recombinant human interleukin-38 and its inhibitory effect on the expression of proinflammatory cytokines in THP-1 cells

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