A possible role of Fas-ligand-mediated "reverse signaling" in pathogenesis of rheumatoid arthritis and systemic lupus erythematosus.
Fas/FasL system is involved in pathogenesis of a variety of autoimmune diseases. In overwhelming majority of situations alterations in Fas and FasL expression are viewed in frames of Fas-mediated apoptosis. In the present work we tested a possible involvement of Fas-ligand-mediated "reverse signaling" in pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We show that high level of sFas in RA patient blood correlates with a high activity of disease; in SLE patients with elevated sFas level there was a correlation between sFas concentration and leucopenia, and tissue and organ damage. We showed for the first time that at high concentrations in serum sFas is present in oligomeric form. Oligomeric sFas demonstrated cytotoxicity in lymphocyte primary culture and in transformed cells, while non-toxic recombinant Fas-ligand partially blocked this effect. Besides, immunohistochemical analysis of PBLs and injured synovia of RA patients revealed the high expression of Fas-ligand. All this together allow assuming the involvement of cytotoxic "reversed signaling" in the pathogenesis of autoimmune diseases.
Telegina
Ekaterina
E
Institute of Molecular Medicine at Sechenov's Moscow Medical Academy, Moscow, Russia.
Reshetnyak
Tatiana
T
Moshnikova
Anna
A
Proussakova
Olga
O
Zhukova
Alexandra
A
Kuznetsova
Alla
A
Ivanov
Alexei
A
Paltsev
Michail
M
Beletsky
Igor
I
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055503:Protein Multimerization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology* / Q000378:metabolism
C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor