Abstract:Enteroviral infections of the heart are among the most commonly identified causes of acute myocarditis in children and adults and have been implicated in dilated cardiomyopathy. Although there is considerable information regarding the cellular immune response in myocarditis, little is known about innate signaling mechanisms within the infected cardiac myocyte that contribute to the host defense against viral infection. Here we show the essential role of Janus kinase (JAK) signaling in cardiac myocyte antiviral… Show more
“…Coxsackievirus usually infects cardiomyocytes and induces the expression of SOCS1 and SOCS3 in cardiomyocytes, which can result in evasion of immune responses and facilitation of virus replication by inhibition of JAK-STAT signaling (32,37). These findings indicate that it may be harmful to administer SOCS1 DNA in the acute phase of infectious myocarditis because it may augment viral replication by inhibition of IFN signaling.…”
Section: Discussionmentioning
confidence: 99%
“…These findings indicate that it may be harmful to administer SOCS1 DNA in the acute phase of infectious myocarditis because it may augment viral replication by inhibition of IFN signaling. The effect of SOCS1 transduction on viral myocarditis has been examined by Yasukawa et al (32). The SOCS1-transgenic mice infected with CVB3 showed increased myocardial injury, virus replication, and mortality.…”
Section: Discussionmentioning
confidence: 99%
“…SOCS1 DNA administration inhibits the development of myocarditis induced by cardiac myosin peptide-loaded BMDC transfer but not by CD4 + T cell transfer Functionally interposed SOCS1 is induced in various cell populations, including leukocytes, vascular cells, and cardiomyocytes (18,31,32). A mouse model of EAM was established by cell transfer using peptide-pulsed DCs or cardiac epitope-specific CD4 + T cells (7,14).…”
Section: In Vivo Socs1 Dna Administration Inhibits DC Functionmentioning
Myocarditis and subsequent dilated cardiomyopathy are major causes of heart failure in young adults. Myocarditis in humans is highly heterogeneous in etiology. Recent studies have indicated that a subgroup of myocarditis patients may benefit from immune-targeted therapies, because autoimmunity plays an important role in myocarditis as well as contributing to the progression to cardiomyopathy and heart failure. Suppressor of cytokine signaling (SOCS) 1 plays a key role in the negative regulation of both TLR- and cytokine receptor-mediated signaling, which is involved in innate immunity and subsequent adaptive immunity. In this study, we investigated the therapeutic effect of SOCS1 DNA administration on experimental autoimmune myocarditis (EAM) in mice. EAM was induced by s.c. immunization with cardiac-specific peptides derived from α myosin H chain in BALB/c mice. In contrast to control myocarditis mice, SOCS1 DNA-injected mice were protected from development of EAM and heart failure. SOCS1 DNA administration was effective for reducing the activation of autoreactive CD4+ T cells by inhibition of the function of Ag-presenting dendritic cells. Our findings suggest that SOCS1 DNA administration has considerable therapeutic potential in individuals with autoimmune myocarditis and dilated cardiomyopathy.
“…Coxsackievirus usually infects cardiomyocytes and induces the expression of SOCS1 and SOCS3 in cardiomyocytes, which can result in evasion of immune responses and facilitation of virus replication by inhibition of JAK-STAT signaling (32,37). These findings indicate that it may be harmful to administer SOCS1 DNA in the acute phase of infectious myocarditis because it may augment viral replication by inhibition of IFN signaling.…”
Section: Discussionmentioning
confidence: 99%
“…These findings indicate that it may be harmful to administer SOCS1 DNA in the acute phase of infectious myocarditis because it may augment viral replication by inhibition of IFN signaling. The effect of SOCS1 transduction on viral myocarditis has been examined by Yasukawa et al (32). The SOCS1-transgenic mice infected with CVB3 showed increased myocardial injury, virus replication, and mortality.…”
Section: Discussionmentioning
confidence: 99%
“…SOCS1 DNA administration inhibits the development of myocarditis induced by cardiac myosin peptide-loaded BMDC transfer but not by CD4 + T cell transfer Functionally interposed SOCS1 is induced in various cell populations, including leukocytes, vascular cells, and cardiomyocytes (18,31,32). A mouse model of EAM was established by cell transfer using peptide-pulsed DCs or cardiac epitope-specific CD4 + T cells (7,14).…”
Section: In Vivo Socs1 Dna Administration Inhibits DC Functionmentioning
Myocarditis and subsequent dilated cardiomyopathy are major causes of heart failure in young adults. Myocarditis in humans is highly heterogeneous in etiology. Recent studies have indicated that a subgroup of myocarditis patients may benefit from immune-targeted therapies, because autoimmunity plays an important role in myocarditis as well as contributing to the progression to cardiomyopathy and heart failure. Suppressor of cytokine signaling (SOCS) 1 plays a key role in the negative regulation of both TLR- and cytokine receptor-mediated signaling, which is involved in innate immunity and subsequent adaptive immunity. In this study, we investigated the therapeutic effect of SOCS1 DNA administration on experimental autoimmune myocarditis (EAM) in mice. EAM was induced by s.c. immunization with cardiac-specific peptides derived from α myosin H chain in BALB/c mice. In contrast to control myocarditis mice, SOCS1 DNA-injected mice were protected from development of EAM and heart failure. SOCS1 DNA administration was effective for reducing the activation of autoreactive CD4+ T cells by inhibition of the function of Ag-presenting dendritic cells. Our findings suggest that SOCS1 DNA administration has considerable therapeutic potential in individuals with autoimmune myocarditis and dilated cardiomyopathy.
“…[21][22][23] The pBSII-aMHC-LOXL-1 vector was constructed by subcloning the human LOXL-1 cDNA (accession no: NM_005576) into the pBSII-aMHC plasmid (generously provided by S Morimoto, Kyushu University). After digestion with SalI, the fragment carrying the aMHC promoter and human LOXL-1 cDNA was microinjected into (C57BL/6 Â C3H) F1 (B6C3-F1) zygotes.…”
Section: Generation Of Cardiac-specific Loxl-1 Transgenic Micementioning
confidence: 99%
“…Mice were anesthetized with isoflurane and subjected to echocardiography as previously described. [22][23][24] Recording was performed as described previously. [22][23][24] …”
Lysyl oxidase (LOX) and LOX-like protein-1 (LOXL-1) are extracellular matrix-embedded amine oxidases that have critical roles in the cross-linking of collagen and elastin. LOX family proteins are abundantly expressed in the remodeled heart of animals and humans and are implicated in cardiac fibrosis; however, their role in cardiac hypertrophy is unknown. In this study, in vitro stimulation with hypertrophic agonists significantly increased LOXL-1 expression, LOX enzyme activity and [ 3 H] leucine incorporation in neonatal rat cardiomyocytes. A LOX inhibitor, beta-aminopropionitrile (BAPN), inhibited agonist-induced leucine incorporation in cardiomyocytes in vitro, suggesting the involvement of LOXL-1 in cardiomyocyte hypertrophy. Abdominal aortic constriction in rats produced left ventricular hypertrophy in parallel with LOXL-1 mRNA upregulation. And BAPN administration significantly inhibited angiotensin II-induced cardiac hypertrophy in vivo. These results suggest a role of LOXL-1 in cardiac hypertrophy in vivo. We generated transgenic mice with cardiomyocyte-specific expression of LOXL-1. LOXL-1 transgenic mice pups were born normally and grew to adulthood without increased mortality; these mice exhibited a greater left ventricle to body weight ratio, larger myocyte diameter, and more brain natriuretic peptide expression than their wild-type littermates. Echocardiography revealed that the LOXL-1 transgenic mice also had greater wall thickness with preserved cardiac contraction. Our results indicate a possible fundamental role of LOXL-1 in cardiac hypertrophy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.