Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle.
Jens Schmidt,Konstanze Barthel,Arne Wrede,Mohammad Salajegheh,Mathias Bähr,Marinos C. Dalakas +5 more
TLDR
The data suggest that, in sIBM muscle, production of high amounts of pro-inflammatory mediators specifically induces β-amyloid-associated degeneration, and may help to design targeted treatment strategies for chronic inflammatory disorders of the skeletal muscle.Abstract:
Distinct interrelationships between inflammation and beta-amyloid-associated degeneration, the two major hallmarks of the skeletal muscle pathology in sporadic inclusion body myositis (sIBM), have remained elusive. Expression of markers relevant for these pathomechanisms were analysed in biopsies of sIBM, polymyositis (PM), dermatomyositis (DM), dystrophic and non-myopathic muscle as controls, and cultured human myotubes. By quantitative PCR, a higher upregulation was noted for the mRNA-expression of CXCL-9, CCL-3, CCL-4, IFN-gamma, TNF-alpha and IL-1 beta in sIBM muscle compared to PM, DM and controls. All inflammatory myopathies displayed overexpression of degeneration-associated markers, yet only in sIBM, expression of the mRNA of amyloid precursor protein (APP) significantly and consistently correlated with inflammation in the muscle and mRNA-levels of chemokines and IFN-gamma. Only in sIBM, immunohistochemical analysis revealed that inflammatory mediators including IL-1 beta co-localized to beta-amyloid depositions within myofibres. In human myotubes, exposure to IL-1 beta caused upregulation of APP with subsequent intracellular aggregation of beta-amyloid. Our data suggest that, in sIBM muscle, production of high amounts of pro-inflammatory mediators specifically induces beta-amyloid-associated degeneration. The observations may help to design targeted treatment strategies for chronic inflammatory disorders of the skeletal muscle.read more
Citations
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Journal ArticleDOI
Inflammatory Muscle Diseases
TL;DR: The four main types of inflammatory muscle disease — dermatomyositis, polymyositis," necrotizing autoimmune myositis", and inclusion-bodyMyositis — are summarized.
Journal ArticleDOI
188th ENMC International Workshop: Inclusion Body Myositis, 2-4 December 2011, Naarden, The Netherlands.
TL;DR: The 188th ENMC workshop titled “Inclusion Body Myositis” was held in Naarden, The Netherlands, 2–4 December 2011 and aimed to build on the work of two previous IBM workshops held in the MRC Centre London 2008 and Paris 2009.
Journal ArticleDOI
Neuroinflammation and Neuronal Loss Precede Aβ Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer’s Disease
Amanda L. Wright,Raphael Zinn,Raphael Zinn,Barbara Hohensinn,Barbara Hohensinn,Lyndsey M. Konen,Sarah B. Beynon,Richard P. Tan,Ian A. Clark,Andrea Abdipranoto,Bryce Vissel,Bryce Vissel +11 more
TL;DR: The possibility that plaque load may not be the best marker for early AD is raised and it is suggested that activated microglia could be a valuable marker to track disease progression.
Journal ArticleDOI
Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease
Zhiyou Cai,Bin Zhao,Anna Ratka +2 more
TL;DR: The mechanism and pathway that oxidative stress contributes to Aβ generation is focused on, which up-regulates Aβ via inducing activity of β- and γ-secretases and increases the BBB permeability.
Journal ArticleDOI
The roles of TNF in brain dysfunction and disease.
TL;DR: This review summarizes the burgeoning literature on cytokines, and how the functions of these molecules, particularly TNF, are influencing the outlook of researchers on the pathophysiology of these diseases, including Alzheimer's disease and other encephalopathies.
References
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Polymyositis and Dermatomyositis
TL;DR: Early initiation of therapy is essential, since both polymyositis and dermatomyositis respond to immunotherapeutic agents and new immunomodulatory agents currently being tested in controlled trials may prove promising for difficult cases.
Polymyositis and dermatomyositis
TL;DR: The time from pneumothorax occurrence to safe resumption of air travel remains controversial and depends on whether pleurodesis was performed and type of lung disease, so individuals with previous pneumothsoraces should be discouraged from diving.
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TNF-α acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle
Yi-Ping Li,Yuling Chen,Joseph John,Jennifer S. Moylan,Bingwen Jin,Douglas L. Mann,Michael B. Reid +6 more
TL;DR: The data suggest that TNF‐α acts via p38 to increase atrogin1/MAFbx gene expression in skeletal muscle, which is similar to what was found with H2O2.
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Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
TL;DR: The data suggest that at ages when the fibrillar plaque pathology is present, C1q exerts a detrimental effect on neuronal integrity, most likely through the activation of the classical complement cascade and the enhancement of inflammation.
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Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies.
TL;DR: The predominant IL-1alpha expression in the blood vessels indicates an importance of the endothelial cells in the inflammatory process in PM, IBM, and DM, and a sustained, local release of T cell-derived cytokines may not be a requirement for tissue injury in theinflammatory myopathies.