The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury

Details

Serval ID
serval:BIB_9CA27B5577EF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury
Journal
Journal of Clinical Investigation
Author(s)
Yasukawa  H., Yajima  T., Duplain  H., Iwatate  M., Kido  M., Hoshijima  M., Weitzman  M. D., Nakamura  T., Woodard  S., Xiong  D., Yoshimura  A., Chien  K. R., Knowlton  K. U.
ISSN
0021-9738 (Print)
Publication state
Published
Issued date
02/2003
Volume
111
Number
4
Pages
469-78
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
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 defense and a negative role of an intrinsic JAK inhibitor, the suppressor of cytokine signaling (SOCS), in the early disease process. Cardiac myocyte-specific transgenic expression of SOCS1 inhibited enterovirus-induced signaling of JAK and the signal transducers and activators of transcription (STAT), with accompanying increases in viral replication, cardiomyopathy, and mortality in coxsackievirus-infected mice. Furthermore, the inhibition of SOCS in the cardiac myocyte through adeno-associated virus-mediated (AAV-mediated) expression of a dominant-negative SOCS1 increased the myocyte resistance to the acute cardiac injury caused by enteroviral infection. These results indicate that strategies directed at inhibition of SOCS in the heart and perhaps other organs can augment the host-cell antiviral system, thus preventing viral-mediated end-organ damage during the early stages of infection.
Keywords
Animals Carrier Proteins/*antagonists & inhibitors/genetics/physiology DNA-Binding Proteins/metabolism Dependovirus/genetics *Enterovirus B, Human/pathogenicity/physiology Enterovirus Infections/etiology/physiopathology/*therapy Gene Therapy Humans *Intracellular Signaling Peptides and Proteins JNK Mitogen-Activated Protein Kinases Mice Mice, Inbred BALB C Mice, Transgenic Mitogen-Activated Protein Kinases/metabolism Models, Biological Myocarditis/etiology/physiopathology/*therapy *Repressor Proteins STAT1 Transcription Factor STAT3 Transcription Factor Signal Transduction Suppressor of Cytokine Signaling Proteins Trans-Activators/metabolism Transfection Virus Replication
Pubmed
Web of science
Create date
25/01/2008 13:44
Last modification date
20/08/2019 15:03
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