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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of injury and death of muscle cells in the inflammatory myopathies (dermatomyositis, polymyositis, and inclusion body myositis) remains obscure. We and others have not detected apoptosis in the muscle biopsies from patients with myositis despite clear evidence of cell damage and loss. We provide evidence in this study that Fas ligand (FasL) as well as Fas is present on muscle cells and inflammatory cells in myositis biopsies: Fas is present on most muscle cells and lymphocytes, and FasL is present on degenerating muscle cells and many infiltrating mononuclear cells. The expression of both Fas and FasL in the inflamed tissue makes the absence of apoptosis more striking. To address the mechanisms of this resistance to classical apoptosis in muscle cells, we have investigated the expression of the antiapoptotic molecule FLICE (Fas-associated death domain-like IL-1-converting enzyme)-inhibitory protein (FLIP) in muscle biopsies of myositis patients and in cultured human skeletal muscle cells. Using laser capture microscopy, we have shown that FLIP is expressed in the muscle fibers and on infiltrating lymphocytes of myositis biopsies. Furthermore, we have shown that FLIP, but not Bcl-2, is expressed in cultured human skeletal muscle cells stimulated with proinflammatory cytokines, and inhibition of FLIP with antisense oligonucleotides promotes significant cleavage of poly(ADP-ribose) polymerase autoantigen, a sensitive indicator of apoptosis. These studies strongly suggest that the resistance of muscle to Fas-mediated apoptosis is due to the expression of FLIP in muscle cells in the inflammatory environment in myositis.
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PMID:The inhibition of apoptosis in myositis and in normal muscle cells. 1079 13

Recent studies have shown an up-regulation of the Fas/Fas ligand system in inflammatory myopathies. In myositis, however, the major Fas-mediated cytotoxicity which activates caspases bypasses apoptosis. We therefore evaluated the expression of proteins promoting cell survival, such as bcl-2, bcl-x(l) and cyclin-dependent kinase inhibitors, on muscle biopsies from 14 patients with polymyositis, dermatomyositis, inclusion body myositis and HIV-associated myositis. Our data demonstrate that inflammatory cells are immunoreactive for bcl-x(l), p16 and p57, three apoptosis-preventing proteins. Hence, we assume that these proteins might protect T cells from apoptotic nuclear changes. Our results could explain the non-self-limiting nature of inflammatory myopathies.
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PMID:T-cell anti-apoptotic mechanisms in inflammatory myopathies. 1106 32