Programmed cell death (PCD) or apoptosis is a highly regulated physiological process which eliminates specific cells from an organism. PCD plays a critical role during embryonic development but is present throughout life. Unregulated or abnormal apoptosis can lead to disease or unwanted tissue destruction. Many tissues, including the salivary gland, express the surface molecule called Fas (CD95) which can deliver an apoptotic signal. Sjogren's syndrome is an autoimmune disease of the exocrine glands that leads to xerostomia and xeropthalmia. Many of the glandular features show evidence of apoptotic destruction. The long term objective of this study is to elucidate the mechanism leading to PCD in the Sj?rgren's syndrome salivary gland.
The Specific Aims are: 1) Study in situ Fas-mediated PCD, bcl-2 family protein expression, the affects of cytokines in the rat salivary gland; 2) Induce with cytokines Fas ligand and bcl-2 family protein expression in the salivary cell lines, (HSY, SMG C6 and SMG C10); 3) determine the role of proapoptotic caspases in rat and human salivary glands; 4) detect in the Sj?rgren's syndrome salivary gland abnormal changes in bcl-2 family member expression. Studies will include immunochemical staining techniques and Western blot Rat parotid and submandibular glands will be cannulated. Cytokines or ant-Fas antibody will be injected into the gland and assessed for apoptosis and PCD associated proteins. Salivary gland cell lines will be cultured with cytokines and studied for apoptosis, Fas-L expression, and bcl-2 family member expression. Gene transfer studies will be performed in vivo and in vitro to regulate Fas ligand and bcl-2 family prtein expression. Caspase inhibitors will be used to identify specific proteases during apoptosis. Biopsy material from patents with Sjogren's syndrome will be immunostained for bcl-2 family member expression.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Health Science Center San Antonio
Internal Medicine/Medicine
Schools of Medicine
San Antonio
United States
Zip Code
Diaz de Guillory, Carolina; Schoolfield, John D; Johnson, Dorthea et al. (2014) Co-relationships between glandular salivary flow rates and dental caries. Gerodontology 31:210-9
Garcia-Carrasco, Mario; Mendoza-Pinto, Claudia; Jimenez-Hernandez, Cesar et al. (2012) Serologic features of primary Sjogren's syndrome: clinical and prognostic correlation. Int J Clin Rheumtol 7:651-659
Jimenez, F; Aiba-Masago, S; Al Hashimi, I et al. (2002) Activated caspase 3 and cleaved poly(ADP-ribose)polymerase in salivary epithelium suggest a pathogenetic mechanism for Sjogren's syndrome. Rheumatology (Oxford) 41:338-42
Aiba-Masago, Sonomi; Liu Xb, Xiao-bing; Masago, Rejei et al. (2002) Bax gene expression alters Ca(2+) signal transduction without affecting apoptosis in an epithelial cell line. Oncogene 21:2762-7
Sun, X; Liu, X B; Martinez, J R et al. (2001) Effects of radiation on Ca2+ signaling in salivary epithelial cell lines transfected with Bcl-2 and Bcl-XL. Eur J Oral Sci 109:103-8
Masago, R; Aiba-Masago, S; Talal, N et al. (2001) Elevated proapoptotic Bax and caspase 3 activation in the NOD.scid model of Sjogren's syndrome. Arthritis Rheum 44:693-702
Aiba-Masago, S; Masago, R; Vela-Roch, N et al. (2001) Fas-mediated apoptosis in a rat acinar cell line is dependent on caspase-1 activity. Cell Signal 13:617-24
Nakabayashi, T; Sakata, K M; Sakata, A et al. (2001) TGF-beta1 null mutation leads to CD154 upregulated expression in affected tissues. Inflammation 25:69-73
Liu, X B; Masago, R; Kong, L et al. (2000) G-protein signaling abnormalities mediated by CD95 in salivary epithelial cells. Cell Death Differ 7:1119-26
Sakata, K; Sakata, A; Kong, L et al. (1999) Monocyte rescue of human T cells from apoptosis is CD40/CD154 dependent. Scand J Immunol 50:479-84