T-cell anti-apoptotic mechanisms in inflammatory myopathies.
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.
Vattemi
G
G
Department of Neurological Sciences and Vision, University of Verona, Verona, Italy.
Tonin
P
P
Filosto
M
M
Spagnolo
M
M
Rizzuto
N
N
Tomelleri
G
G
D017209:Apoptosis / Q000276:immunology*; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000276:immunology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000032:analysis / Q000276:immunology; D003882:Dermatomyositis / Q000276:immunology / Q000473:pathology; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000276:immunology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000276:immunology / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000276:immunology; D017285:Polymyositis / Q000276:immunology* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; D019014:fas Receptor / Q000032:analysis / Q000276:immunology
C494811:BCL2L1 protein, human; D017252:CD3 Complex; C493956:CDKN1A protein, human; C493964:CDKN1C protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; D019014:fas Receptor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases