Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011633 (dermatomyositis)
 4,181 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to explore the role of interleukin (IL)-18 in patients with inflammatory myopathies (IM) such as dermatomyositis (DM) and polymyositis (PM) in relation to the possible predominance of a Th1 immune response in their pathogenesis. Serum concentrations of IL-18, interferon (IFN)-gamma, IL-4 and IL-6 were measured in six patients by enzyme-linked immunosorbent assay (ELISA). IL-18 expression was evaluated by in situ hybridization (ISH), whereas CD68, CD8 and CD83 were investigated by immunohistochemistry (IHC) to define the main producers of IL-18. Lastly, the expression of both IL-18 receptor (IL-18R) and monocyte chemoattractant protein (MCP)-1 was also explored by IHC. High serum levels of IL-18 and IFN-gamma, and conversely low titres of IL-4 and IL-6, were demonstrated in both diseases. In addition, IL-18 was overexpressed in muscle biopsy specimens from patients with IM. Both macrophages and dendritic cells (DC) surrounding either perivascular and perimysium areas in DM or endomysium in PM were the main producers of IL-18. Endothelial cells (EC), smooth muscle cells (SMC) and CD8(+) T cells expressed a high content of IL-18R. Vessel cells overexpressed MCP-1 in parallel with IL-18R. High concentrations of serum IL-18 as well as muscular up-regulation of IL-18 and IL-18R suggest that deregulation of the IL-18/IL-18R pathway is a pathogenetic mechanism in IM. Measurement of IL-18 may thus predict the severity of both DM and PM.
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PMID:Interleukin-18 overexpression as a hallmark of the activity of autoimmune inflammatory myopathies. 1696 94

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.
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PMID:Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle. 1866 3

Distinct mechanisms such as humeral immunity in dermatomyositis (DM) and T-cell-mediated cytotoxicity in polymyositis (PM) contribute to the pathology of inflammatory myopathies. In addition, different subsets of macrophages are present in both diseases. Herein, the characteristics of 25F9-positive macrophages in skeletal muscle inflammation are outlined. Muscle biopsies of subjects with DM and PM were studied by immunohistochemical multi-labelling using the late-activation marker 25F9, together with markers characterizing macrophage function including IFN-gamma, iNOS, and TGF-beta. In PM, a robust expression of IFN-gamma, iNOS, and TGF-beta was observed in inflammatory cells. Double- and serial-labelling revealed that a subset of 25F9-positive macrophages in the vicinity of injured muscle fibres expressed iNOS and TGF-beta, but not IFN-gamma. In DM, IFN-gamma, iNOS and TGF-beta were also expressed in inflammatory cells in the endomysium. Double- and serial-labelling studies in DM indicated that 25F9-positive macrophages expressed TGF-beta and to a lesser degree iNOS, but not IFN-gamma. In conclusion, our data suggest that late-activated macrophages contribute to the pathology of inflammatory myopathies.
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PMID:Distinct inflammatory properties of late-activated macrophages in inflammatory myopathies. 1936 61

Interstitial lung disease (ILD) may be associated with systemic inflammatory disorders and autoantibody production. The development of ILD has been described in detail in patients with polymyositis and dermatomyositis. Anti-synthetase antibodies, including anti-Jo-1 antibodies (antihistidyl-tRNA syntase), are found in up to 35 % of patients with myositis, 80 % of which constitute anti-Jo-1 antibodies. The anti-Jo-1 syndrome characteristically presents with myositis, shortness of breath, fever, polyarthritis/arthralgia, mechanic's hands, dermatomyositis-like skin lesions, signs of a connective tissue disease and/or Raynaud's phenomenon. ILD is an early diagnostic sign and shows focal infiltrates and an acinar pattern in CT scan. Non-specific interstitial pneumonitis with T-lymphocytic infiltrates in lung histology (VATS) or elevated IFN-gamma-inducible chemokines are further indicators for anti-Jo-1 syndrome. Corticosteroids eventually combined with an immunosuppressant drug are often required with reported beneficial effects, although not many therapeutic studies have been performed. Here we present a review of the current literature and a case report on anti-Jo-1 syndrome.
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PMID:[The anti-Jo-1 syndrome - a specific form of myositis with interstitial lung disease]. 2038 95


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