Overexpression of the apoptosis inhibitor FLIP in T cells correlates with disease activity in multiple sclerosis.
The cellular caspase-inhibitory protein FLIP has been recently identified as a potent regulator of T lymphocyte susceptibility to Fas-mediated programmed cell death (apoptosis). Since impairment of apoptosis may be involved in multiple sclerosis (MS), we investigated the dynamics of cellular FLIP in unstimulated and activated T lymphocytes from MS patients, inflammatory and non-inflammatory neurological disorders, and healthy subjects. Cellular expression of the long and short forms of FLIP protein was similar in unstimulated T cells from MS patients and controls, but was significantly higher in activated T cells from patients with clinically active MS. This high FLIP expression in active MS correlated with cellular resistance to Fas-mediated apoptosis. In contrast, cellular expression of the anti-apoptotic protein Bcl-2 did not differ between active and stable disease, and was relatively similar between the MS group and controls. These findings suggest that cellular overexpression of the anti-apoptotic protein FLIP is a feature of clinically active multiple sclerosis.
Semra
Y K
YK
Department of Neuroimmunology, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, SE1 9RT, London, UK.
Seidi
O A
OA
Sharief
M K
MK
D017209:Apoptosis / Q000502:physiology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism / Q000503:physiopathology*; D009422:Nervous System Diseases / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012016:Reference Values; D013601:T-Lymphocytes / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor