IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK. (12th January 2017)

• Record Type: Journal Article
• Authors: Schmidt, Karsten; Wienken, Magdalena; Keller, Christian W.; Balcarek, Peter; Münz, Christian; Schmidt, Jens
• Other Names: Amedei Amedeo Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2017(2017)
• Publication Date: 2017-01-12
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2017/5470831
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : 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-1 β 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-1 β 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.