Autoantibodies from Sjögren's syndrome induce activation of both the intrinsic and extrinsic apoptotic pathways in human salivary gland cell line A-253.
Sjögren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary and lachrymal glands, characterized by a high concentration of serum autoantibodies directed against nuclear and cytoplasmic antigens. It is known that autoantibodies can enter viable cells and this phenomenon has functional consequences including activation of apoptotic process. The objective of this work was to explore whether autoantibodies contained in IgG purified from Sjögren sera trigger apoptotic process in an experimental model represented by the human salivary gland cell line A-253. To define if the intrinsic or extrinsic pathways are activated, we examined which caspases are critical for inducing cell death. The results have demonstrated that morphological changes and DNA laddering, consistent with apoptotic cell death, occurred in A-253 cells treated with IgG from Sjögren sera. Sjögren IgG induced cleavage and activation of the effector caspase-3 and degradation of the caspase-3 substrate poly(ADP-ribose)polymerase. Both the intrinsic and extrinsic apoptotic pathways were activated, since both caspase-8 and caspase-9 cleavages occurred. In conclusion, autoantibodies contained in IgG purified from Sjögren sera mediate apoptosis of the A-253 cell line in a caspase-dependent manner.
Sisto
M
M
Department of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 1, Policlinico, I-70124 Bari, Italy. m.sisto@anatomia.uniba.it
Lisi
S
S
Castellana
D
D
Scagliusi
P
P
D'Amore
M
M
Caprio
S
S
Scagliusi
A
A
Acquafredda
A
A
Panaro
M A
MA
Mitolo
V
V
D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood / Q000502:physiology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007074:Immunoglobulin G; D012469:Salivary Glands / Q000166:cytology*; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases