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http://purl.uniprot.org/citations/27578244http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27578244http://www.w3.org/2000/01/rdf-schema#comment"Muscle wasting is a common feature of inflammatory myopathies. Glucocorticoids (GCs), although effective at suppressing inflammation and inflammatory muscle loss, also cause myopathy with prolonged administration. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bidirectional GC-activating enzyme that is potently upregulated by inflammation within mesenchymal-derived tissues. We assessed the regulation of this enzyme with inflammation in muscle, and examined its functional impact on muscle. The expression of 11β-HSD1 in response to proinflammatory stimuli was determined in a transgenic murine model of chronic inflammation (TNF-Tg) driven by overexpression of tumour necrosis factor (TNF)-α within tissues, including muscle. The inflammatory regulation and functional consequences of 11β-HSD1 expression were examined in primary cultures of human and murine myotubes and human and murine muscle biopsies ex vivo. The contributions of 11β-HSD1 to muscle inflammation and wasting were assessed in vivo with the TNF-Tg mouse on an 11β-HSD1 null background. 11β-HSD1 was significantly upregulated within the tibialis anterior and quadriceps muscles from TNF-Tg mice. In human and murine primary myotubes, 11β-HSD1 expression and activity were significantly increased in response to the proinflammatory cytokine TNF-α (mRNA, 7.6-fold, p < 0.005; activity, 4.1-fold, p < 0.005). Physiologically relevant levels of endogenous GCs activated by 11β-HSD1 suppressed proinflammatory cytokine output (interkeukin-6, TNF-α, and interferon-γ), but had little impact on markers of muscle wasting in human myotube cultures. TNF-Tg mice on an 11β-11β-HSD1 knockout background developed greater muscle wasting than their TNF-Tg counterparts (27.4% less; p < 0.005), with smaller compacted muscle fibres and increased proinflammatory gene expression relative to TNF-Tg mice with normal 11β-HSD1 activity. This study demonstrates that inflammatory stimuli upregulate 11β-HSD1 expression and GC activation within muscle. Although concerns have been raised that excess levels of GCs may be detrimental to muscle, in this inflammatory TNF-α-driven model, local endogenous GC activation appears to be an important anti-inflammatory response that protects against inflammatory muscle wasting in vivo. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.org/dc/terms/identifier"doi:10.1002/path.4806"xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Buckley C.D."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Raza K."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Hussain Z."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Naylor A."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"O'Leary M."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Stewart P.M."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Jones S.W."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Lavery G.G."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Cooper M.S."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Filer A."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Hardy R.S."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Morgan S.A."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Doig C.L."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/author"Pearson M.J."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/name"J Pathol"xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/pages"472-483"xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/title"11beta-Hydroxysteroid dehydrogenase type 1 within muscle protects against the adverse effects of local inflammation."xsd:string
http://purl.uniprot.org/citations/27578244http://purl.uniprot.org/core/volume"240"xsd:string
http://purl.uniprot.org/citations/27578244http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27578244
http://purl.uniprot.org/citations/27578244http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27578244
http://purl.uniprot.org/uniprot/#_A0A0G2JGF4-mappedCitation-27578244http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27578244
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