Induction of a broad spectrum of inflammation-related genes by Coxsackievirus B3 requires Interleukin-1 signaling

Rehren, Fabienne; Ritter, Barbara; Dittrich–Breiholz, Oliver; Henke, Andreas; Lam, Elena; Kati, Semra; Heim, Albert

doi:10.1007/s00430-012-0245-2

Cited by 13 publications

(6 citation statements)

References 68 publications

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“…How much inflammatory response contributes to myocardial injury and whether tissue alteration could be avoided by a more rapid decline of inflammation is currently unknown [2]. As reported previously, mediators that may play a role in the pathogenesis of the CVB-induced myocarditis include proinflammatory cytokines such as TNF-α and IL-6 [15][16][17][18] and MMPs [19,20]. In addition, studies showed that in different cardiac-related pathologic conditions, cardiomyocytes were actively involved in cytokine biosynthesis [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence highlighted the immunopathogenetic mechanisms responsible for the development of CVB-induced myocarditis and focused on mediators that may play a role in the pathogenesis of the disease including the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) [15][16][17][18] and matrix metalloproteinases (MMPs) [19,20]. Furthermore, in the past, studies showed that in different cardiac-related pathologic conditions, such as ischemic heart disease, congestive heart failure, dilated cardiomyopathy, septic cardiomyopathy and myocarditis, cardiomyocytes were actively involved in cytokine biosynthesis [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Synthetic Anti-Inflammatory Sterol in CB3V-Induced Myocarditis: A Morphological Study on Heart Muscle Tissue

Castrogiovanni

Trovato

Szychlinska

et al. 2016

JFMK

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Cell-mediated immune events play a role in the pathogenesis of myocarditis provoked by Group B coxsackievirus (CVB). Studies indicated the synthetic derivative of androstene-3β,7β,17βtriol, HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol), may ameliorate the course of immunoinflammatory and autoimmune diseases in rodents. The aim of this study was to evaluate effects of HE3286 on histological signs of CVB-induced myocarditis. BALB/c mice were infected with coxsackie B3 virus (CB3V) and treated by intraperitoneal administration of dexamethasone (Dex) or by oral gavage with HE3286 or with its vehicle, HERF405, for 18 days. Mice were sacrificed and hearts were explanted for histological and immunohistochemical analysis (TNF-α, IL-6, MMP9, ADAM10 and HSP-70). Heart tissues of Dex-treated mice showed a better histological structure compared with mice treated with HERF405. An almost complete resolution of myocarditis was observed in HE3286-treated mice as evidenced by lack of inflammatory infiltration. Immunohistochemical findings confirmed HE3286 had a more pronounced effect than Dex in reducing inflammatory response associated with in situ modulation of cytokine expression and tissue remodeling. Our data demonstrate HE3286 has better results in inhibiting establishment and progression of murine CVB-induced myocarditis than Dex, suggesting this drug may also have a therapeutic role in treatment of CVB-induced myocarditis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Synthetic Anti-Inflammatory Sterol in CB3V-Induced Myocarditis: A Morphological Study on Heart Muscle Tissue

Castrogiovanni

Trovato

Szychlinska

et al. 2016

JFMK

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“…First strand cDNA synthesis was carried out using Super Script II (Invitrogen, Carlsbad, CA), dNTP's (Promega, Madison, WI) and Random Hexamer Primers (Fermentas, Burlington, ON). Real‐time PCR was performed in a total volume of 25 µl using Brilliant SYBR Green QPCR in an Mx 3000P instrument (Agilent Technologies, Santa Clara, CA) as described previously [Rehren et al, ]. Intron spanning primer pairs for HAdV‐B3 (E1A and hexon gene) and for HAdV‐C2 (E1A, E1B, DNA polymerase and hexon gene) are described in Table .…”

Section: Methodsmentioning

confidence: 99%

Type dependent patterns of human adenovirus persistence in human T‐lymphocyte cell lines

Markel

Lam

Harste

et al. 2013

Journal of Medical Virology

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Disseminated adenovirus infections cause significant mortality in stem cell transplanted patients and are suspected to originate from asymptomatic adenovirus persistence ("latency") in lymphocytes. The infection of three human T-lymphocyte lines (Jurkat, PM1, and CEM) with human adenovirus types of species A (HAdV-A31), B (HAdV-B3, -B11), and C (HAdV-C2, -C5) was investigated for 150 days in order to establish in vitro models for adenovirus persistence. HAdV-C5 persisted with continuous production of infectious virus progeny (about 10(7) TCID50 /ml) in PM1 cells. More than 100 copies of HAdV-C5-DNA per cell were detected by real-time PCR but hexon immunostaining showed that only 7.5% of the cells were infected ("carrier state infection"). Coxsackie and adenovirus receptor (CAR) expression was decreased in comparison to mock infected cultures suggesting selection of a semi-permissive subpopulation of PM-1 cells. By contrast, latency of HAdV-DNA (10(-3) -10(-4) copies/cell) without production of infectious virus progeny was observed in HAdV-C2 infection of PM1 and Jurkat, HAdV-A31 infection of PM1, and HAdV-B3 infection of Jurkat cells. In addition, transcription of E1A, DNA polymerase and hexon mRNA was not detected by RT-PCR suggesting an equivalent of clinical "HAdV latency." Persistence of HAdV-DNA was not observed in abortive infections of PM1 cells with HAdV-B3 and -B11 and in productive, lytical infections of Jurkat cells with HAdV-C5, HAdV-B11, and HAdV-A31. In conclusion, lytic and persistent infections with and without production of infectious virus were observed depending on the type of adenovirus. Genetic determinants for viral persistence may be investigated using these newly established infection models.

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“…Among the cytokines, increased IL-1␤ levels in the heart directly correlate with increased acute CVB3-induced myocarditis in murine model (9,29). Furthermore, a broad spectrum of inflammatory cytokines is induced by CVB3 replication via a pathway that requires IL-1 signaling (18,38). Inflammasome is a key modulator of inflammatory responses via regulating IL-1␤ release and has been demonstrated to be involved in a wide variety of inflammatory and autoimmune diseases; however, its role in CVB3-induced myocarditis is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis

Wang

Gao

Xiong

2014

American Journal of Physiology-Heart and Circulatory Physiology

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Viral myocarditis, which is most prevalently caused by coxsackievirus B3 (CVB3) infection, is a serious clinical condition characterized by cardiac inflammation. Inflammasome plays an essential role in the regulation of diverse inflammatory responses by serving as a platform for caspase-1 activation and caspase-1-dependent proteolytic maturation and secretion of IL-1␤. Although inflammasome has been reported to be crucial for the development of many inflammatory diseases, its role in the pathogenesis of viral myocarditis is still elusive. The present study aims to investigate whether CVB3 infection activates inflammasome and whether the activation of inflammasome contributes to CVB3-induced myocarditis. Our results showed that CVB3 infection induced inflammasome activation both in vitro and in vivo. With the inhibition of inflammasome activation, the severity of CVB3-induced myocarditis was significantly alleviated as evidenced by less weight loss, decreased serological indexes of creatine kinase and creatine kinase-MB activities, as well as less severe myocardial injury. Of importance, echocardiography results showed that inhibition of inflammasome activation also efficiently improved cardiac function as revealed by enhanced left ventricular ejection fraction and left ventricular fractional shortening. Despite that CVB3 infection significantly increased the expression of both retinoic acid-inducible gene 1 and NOD-like receptor family, pyrin domain containing 3 (NLRP3) in cardiac myocytes, CVB3-induced inflammasome activation was NLRP3-, but not retinoic acid-inducible gene 1, dependent. Further study showed that reactive oxygen species production and K ϩ efflux were critical for the activation of NLRP3 inflammasome upon CVB3 infection. Collectively, our study demonstrated a crucial role of the NLRP3 inflammasome in the pathogenesis of CVB3-induced myocarditis, and modulation of inflammasome activation might represent a promising therapeutic strategy for viral myocarditis. coxsackievirus B3; viral myocarditis; inflammasome; interleukin-1␤; NLRP3

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Induction of a broad spectrum of inflammation-related genes by Coxsackievirus B3 requires Interleukin-1 signaling

Abstract: A broad spectrum of inflammatory cytokines was induced by CVB3 replication via a pathway that requires IL-1 signaling. Our results suggest that IL-1ra may be used as a therapeutic agent to limit inflammation and tissue destruction in myocarditis.

Cited by 13 publications

References 68 publications

Effects of Synthetic Anti-Inflammatory Sterol in CB3V-Induced Myocarditis: A Morphological Study on Heart Muscle Tissue

Effects of Synthetic Anti-Inflammatory Sterol in CB3V-Induced Myocarditis: A Morphological Study on Heart Muscle Tissue

Type dependent patterns of human adenovirus persistence in human T‐lymphocyte cell lines

Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis

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