IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK

The pathology of inclusion body myositis (IBM) involves an inflammatory response and β-amyloid deposits in muscle fibres. It is believed that MAP kinases such as the ERK signalling pathway mediate the inflammatory signalling in cells. Further, there is evidence that autophagic activity plays a cruci...

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Main Authors: Karsten Schmidt, Magdalena Wienken, Christian W. Keller, Peter Balcarek, Christian Münz, Jens Schmidt
Format: Article
Language:English
Published: Hindawi Limited 2017-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2017/5470831
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spelling doaj-a650932174d4475b82ae0ae34fea6d942020-11-25T01:08:16ZengHindawi LimitedMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/54708315470831IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERKKarsten Schmidt0Magdalena Wienken1Christian W. Keller2Peter Balcarek3Christian Münz4Jens Schmidt5Department of Neurology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Neurology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Neurology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Göttingen, GermanyInstitute of Experimental Immunology, Laboratory of Viral Immunobiology, University of Zürich, Zürich, SwitzerlandDepartment of Neurology, University Medical Center Göttingen, Göttingen, GermanyThe pathology of inclusion body myositis (IBM) involves an inflammatory response and β-amyloid deposits in muscle fibres. It is believed that MAP kinases such as the ERK signalling pathway mediate the inflammatory signalling in cells. Further, there is evidence that autophagic activity plays a crucial role in the pathogenesis of IBM. Using a well established in vitro model of IBM, the autophagic pathway, MAP kinases, and accumulation of β-amyloid were examined. We demonstrate that stimulation of muscle cells with IL-1β and IFN-γ led to an increased phosphorylation of ERK. The ERK inhibitor PD98059 diminished the expression of proinflammatory markers as well as the accumulation of β-amyloid. In addition, IL-1β and IFN-γ led to an increase of autophagic activity, upregulation of APP, and subsequent accumulation of β-sheet aggregates. Taken together, the data demonstrate that the ERK pathway contributes to formation of β-amyloid and regulation of autophagic activity in muscle cells exposed to proinflammatory cell stress. This suggests that ERK serves as an important mediator between inflammatory mechanisms and protein deposition in skeletal muscle and is a crucial element of the pathology of IBM.http://dx.doi.org/10.1155/2017/5470831
collection DOAJ
language English
format Article
sources DOAJ
author Karsten Schmidt
Magdalena Wienken
Christian W. Keller
Peter Balcarek
Christian Münz
Jens Schmidt
spellingShingle Karsten Schmidt
Magdalena Wienken
Christian W. Keller
Peter Balcarek
Christian Münz
Jens Schmidt
IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK
Mediators of Inflammation
author_facet Karsten Schmidt
Magdalena Wienken
Christian W. Keller
Peter Balcarek
Christian Münz
Jens Schmidt
author_sort Karsten Schmidt
title IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK
title_short IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK
title_full IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK
title_fullStr IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK
title_full_unstemmed IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK
title_sort il-1β-induced accumulation of amyloid: macroautophagy in skeletal muscle depends on erk
publisher Hindawi Limited
series Mediators of Inflammation
issn 0962-9351
1466-1861
publishDate 2017-01-01
description The pathology of inclusion body myositis (IBM) involves an inflammatory response and β-amyloid deposits in muscle fibres. It is believed that MAP kinases such as the ERK signalling pathway mediate the inflammatory signalling in cells. Further, there is evidence that autophagic activity plays a crucial role in the pathogenesis of IBM. Using a well established in vitro model of IBM, the autophagic pathway, MAP kinases, and accumulation of β-amyloid were examined. We demonstrate that stimulation of muscle cells with IL-1β and IFN-γ led to an increased phosphorylation of ERK. The ERK inhibitor PD98059 diminished the expression of proinflammatory markers as well as the accumulation of β-amyloid. In addition, IL-1β and IFN-γ led to an increase of autophagic activity, upregulation of APP, and subsequent accumulation of β-sheet aggregates. Taken together, the data demonstrate that the ERK pathway contributes to formation of β-amyloid and regulation of autophagic activity in muscle cells exposed to proinflammatory cell stress. This suggests that ERK serves as an important mediator between inflammatory mechanisms and protein deposition in skeletal muscle and is a crucial element of the pathology of IBM.
url http://dx.doi.org/10.1155/2017/5470831
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