Autoantibodies from Sjögren's syndrome trigger apoptosis in salivary gland cell line.
The presence of serum autoantibodies has been associated with Sjögren's syndrome (SS), an autoimmune rheumatic disease that targets salivary and lachrymal glands. The association of apoptosis with autoantibodies production seems to play a role in the pathogenesis of glandular damage. The best-defined antibodies in SS are those reacting with the ribonucleoprotein antigens SS-A (Ro) and SS-B (La). Anti-Ro antibodies are found in about 70-90%, and anti-La in approximately the same frequency, of patients with primary SS. The objective of this work was to explore whether anti-Ro and anti-La autoantibodies purified from Sjögren IgG fractions are able to trigger apoptotic process in the human salivary gland cell line A-253. Anti-Ro and anti-La autoantibodies were purified on protein G Sepharose affinity column and used for the A-253 cell treatment. Apoptosis induced by autoantibodies was revealed by FACS analysis, and the active caspase-3 and the cleaved caspase-3 substrate poly (ADP-ribose) polymerase (PARP) was demonstrated by colorimetric assay and Western blot. This report shows that anti-Ro and anti-La autoantibodies, but not healthy IgG, activate the caspase-3 and determine the cleavage of PARP in A-253 cells. Apoptosis triggered by Sjögren autoantibodies could be responsible for the impairment of the secretory function in the salivary glands.
Sisto
Margherita
M
Department of Human Anatomy and Histology, University of Bari, I-70124 Bari, Italy. m.sisto@anatomia.uniba.it
Lisi
Sabrina
S
Lofrumento
Dario
D
D'Amore
Massimo
M
Scagliusi
Pasquale
P
Mitolo
Vincenzo
V
D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology* / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; C035356:SS-A antibodies; C035357:SS-B antibodies; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3