Interferon‐stimulated gene 15 (<i>ISG15</i>) conjugates proteins in dermatomyositis muscle with perifascicular atrophy

Salajegheh, Mohammad; Kong, Sek Won; Pinkus, Jack L.; Walsh, Ronan J.; Liao, Anne P.; Nazareno, Remedios; Amato, Anthony A.; Krastins, Bryan; Morehouse, Chris; Higgs, Brandon W.; Jallal, Bahija; Yao, Yihong; Sarracino, David; Parker, Kenneth C.; Greenberg, Steven A.

doi:10.1002/ana.21805

Cited by 158 publications

(161 citation statements)

References 41 publications

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“…In a recent study on dermatomyositis, an autoimmune disorder involving skeletal muscle, the ISG15 pathway was associated with atrophy (26). In light of our results, further investigation into the link between type I IFN response and myocyte damage may prove fruitful.…”

Section: Role Of Chemokines Cytokines Adhesion Molecules and Myd88supporting

confidence: 54%

Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure

Maier

Schips²,

Wietelmann³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

156

113

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Inflammation is a major factor in heart disease. IκB kinase (IKK) and its downstream target NF-κB are regulators of inflammation and are activated in cardiac disorders, but their precise contributions and targets are unclear. We analyzed IKK/NF-κB function in the heart by a gain-of-function approach, generating an inducible transgenic mouse model with cardiomyocyte-specific expression of constitutively active IKK2. In adult animals, IKK2 activation led to inflammatory dilated cardiomyopathy and heart failure. Transgenic hearts showed infiltration with CD11b + cells, fibrosis, fetal reprogramming, and atrophy of myocytes with strong constitutively active IKK2 expression. Upon transgene inactivation, the disease was reversible even at an advanced stage. IKK-induced cardiomyopathy was dependent on NF-κB activation, as in vivo expression of IκBα superrepressor, an inhibitor of NF-κB, prevented the development of disease. Gene expression and proteomic analyses revealed enhanced expression of inflammatory cytokines, and an IFN type I signature with activation of the IFN-stimulated gene 15 (ISG15) pathway. In that respect, IKK-induced cardiomyopathy resembled Coxsackievirus-induced myocarditis, during which the NF-κB and ISG15 pathways were also activated. Vice versa, in cardiomyocytes lacking the regulatory subunit of IKK (IKKγ/NEMO), the induction of ISG15 was attenuated. We conclude that IKK/NF-κB activation in cardiomyocytes is sufficient to cause cardiomyopathy and heart failure by inducing an excessive inflammatory response and myocyte atrophy.transcription factors | transgenic mice

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Section: Role Of Chemokines Cytokines Adhesion Molecules and Myd88supporting

confidence: 54%

Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure

Maier

Schips²,

Wietelmann³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

156

113

View full text Add to dashboard Cite

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“…The release of other cytokines and soluble mediators such as TNF and NO by the activated T and B cells may further enhance the inflammatory processes taking place in the muscle [4]. Multiple findings indicate that upregulation of the Type 1 interferon pathway plays a prominent role in the disease pathogenesis in DM [26,27]although it is not specific to DM [29].…”

Section: Dermatomyositismentioning

confidence: 99%

“…Microarray gene expression profiling has detected upregulation of genes for adhesion molecules, cytokines, MHC class I molecules, chemokines and immunoglobulins in the muscles of patients with inflammatory myopathies [4,[53][54][55][56].In particular, the interferons (IFNs)and IFN-inducible genes have been strongly implicated in the pathogenesis of myositis. The enhanced type I IFN gene signature has been associated with disease activity in both PM and DM [57].Additionally,immunostaining for type I IFN has been detected in DM in muscle fibres in areas showingperifascular atrophy, as well as in plasmacytoid dendritic cells and in the capillary endothelial cells [27,58]. In contrast,overexpression of the type IIIFN (IFN-ƴ)…”

Section: 4cytokine and Chemokine Involvementmentioning

confidence: 99%

The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

Moran

Mastaglia

2014

Neuromuscular Disorders

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The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications. Neuromuscular Disorders, 24 (11) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Recent microarray studies have pointed toward a mechanism of tissue injury associated with the overexpression of type 1 interferoninducible gene [123,124]. Interferon-stimulated gene 15 (ISG15) conjugated proteins in DM muscle with muscle perifascicular atrophy, were investigated by Salajeheh et al [123].…”

Section: Dermatomyositis With Muscle Perifascicular Atrophymentioning

confidence: 99%

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

Gelfi

Vasso

Cerretelli

2011

Journal of Proteomics

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Interferon‐stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy

Cited by 158 publications

References 41 publications

Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure

Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure

The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

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