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Rheumatology 2002; 41: 338-342
© 2002 British Society for Rheumatology

Original Papers

Activated caspase 3 and cleaved poly(ADP-ribose)polymerase in salivary epithelium suggest a pathogenetic mechanism for Sjögren's syndrome

F. Jimenez, S. Aiba-Masago, I. Al Hashimi1, N. Vela-Roch, G. Fernandes, C.-K. Yeh2, N. Talal3 and H. Dang

2 Departments of Medicine and Dental Diagnostic Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Texas,
1 Baylor College of Dentistry, Dallas, Texas and
3 Columbia University College of Physicians & Surgeons, New York, NY, USA

Objective. Apoptosis is an organized energy-dependent process of cellular self-destruction carried out by proteolytic enzymes such as the caspases. These enzymes may play a role in epithelial cell apoptosis in Sjögren's syndrome (SS). A classical caspase substrate is poly(ADP-ribose)polymerase (PARP), a DNA repair enzyme. To elucidate the molecular mechanisms responsible for salivary gland dysfunction in SS, we studied the expression of caspase and PARP in SS salivary gland biopsies.

Methods. The presence of activated caspases (caspases 3 and 9) and cleaved PARP (85 kDa) in SS biopsies was demonstrated by immunohistochemistry using specific polyclonal antibodies.

Results. Initial studies performed with an antibody reagent that recognizes both active and inactive forms of caspase 3 identified this enzyme in SS salivary ductal and acinar cells. Activated caspase 3 and cleaved PARP were strongly expressed in ductal and acinar cells in SS salivary glands (13/15). Ductal and acinar cells from normal salivary glands (n=5) stained with less intensity compared with SS tissue. Staining for activated caspase 9 was negative in all samples. Likewise, infiltrating lymphocytes were negative for caspase 3, caspase 9 and cleaved PARP.

Conclusion. This study shows that caspase 3 is important in the salivary dysfunction of SS, while caspase 9 appears not to be involved.

KEY WORDS: Sjögren's syndrome, Apoptosis, Salivary gland, Caspase, CD95, Epithelial cells.

Correspondence to: H. Dang, Department of Community Dentistry, Mail Code 7917, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.


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