Decreased levels of CD95 and caspase-8 mRNA in multiple sclerosis patients with gadolinium-enhancing lesions on MRI.
Magnetic resonance imaging (MRI) allows examining inflammation and central nervous system (CNS) tissue damage in patients suffering from multiple sclerosis (MS), a demyelinating disease of the CNS. Using real-time PCR, we quantified mRNA levels of apoptosis regulators CD95, CD95 ligand, caspase-8, -10 and cellular FLICE-inhibitory protein (cFLIP), and cytokines IL-10 and TNF-alpha in blood mononuclear cells of MS patients at the time of MRI examination. Patients with detectable gadolinium-enhancing lesions had lower expression of CD95 and caspase-8 (P<0.05). Lesion load and brain atrophy did not correlate with expression levels of any of the target molecules studied. Disease duration correlated positively with both FLIP/caspase-8 and CD95/CD3 ratios (P<0.05). These results support the notion that the CD95-dependent pathway plays a complex role in the regulation of survival of activated immune cells in MS.
Gomes
Andreia C
AC
Division of Neurology, Neurotec Department, Karolinska Institute, Huddinge University Hospital R54, SE-141 86 Stockholm, Sweden. andreia.gomes@neurotec.ki.se
Morris
Michael
M
Stawiarz
Leszek
L
Jönsson
Gun
G
Putheti
Prabhakar
P
Bronge
Lena
L
Link
Hans
H
Hillert
Jan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D005260:Female; D005682:Gadolinium; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D018709:Statistics, Nonparametric; D019014:fas Receptor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*
D012333:RNA, Messenger; D019014:fas Receptor; D005682:Gadolinium; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases