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...

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Bibliographic Details
Published in:Journal of autoimmunity 2006-08, Vol.27 (1), p.38-49
Main Authors: Sisto, M., Lisi, S., Castellana, D., Scagliusi, P., D'Amore, M., Caprio, S., Scagliusi, A., Acquafredda, A., Panaro, M.A., Mitolo, V.
Format: Article
Language:English
Subjects:
Apoptosis
Autoantibodies - blood
Autoantibodies - physiology
Autoantibody
Biological and medical sciences
Caspase
Caspase 3
Caspase 8
Caspase 9
Caspases - metabolism
Cell Line
Fundamental and applied biological sciences. Psychology
Fundamental immunology
General aspects
Humans
Immunoglobulin G
Immunopathology
Medical sciences
PARP
Salivary Glands - cytology
Signal Transduction
Sjogren's Syndrome - immunology
Sjögren's syndrome
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Summary: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.
ISSN:0896-8411
1095-9157
DOI:10.1016/j.jaut.2006.05.001