Increased cellular expression of the caspase inhibitor FLIP in intrathecal lymphocytes from patients with multiple sclerosis.
Failure of Fas-mediated apoptosis of potentially pathogenic, autoreactive T lymphocytes may be involved in the pathogenesis of multiple sclerosis. The intracellular protein FLIP, a naturally occurring caspase-antagonist, is a potent inhibitor of the Fas signalling pathway that may block Fas-mediated apoptosis of activated lymphocytes. This study reports specific overexpression of both long and short forms of FLIP in intrathecal lymphocytes from patients with multiple sclerosis. The overexpression of FLIP is independent of cellular expressions of Fas receptor or the anti-apoptotic protein Bcl-2. These results provide a better understanding of some of the intrinsic immunoregulatory mechanisms that are involved in multiple sclerosis.
Sharief
M K
MK
Department of Neuroimmunology, Guy's, King's and St. Thomas' School of Medicine, Hodgkin Building, Guy's Hospital, SE1 9RT, London, UK. m.sharief@umds.ac.uk
D000293:Adolescent; D000328:Adult; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000096:biosynthesis*; D061945:Caspase Inhibitors; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000276:immunology; D019014:fas Receptor / Q000032:analysis / Q000096:biosynthesis
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor