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Int. J. Mol. Sci. 2018, 19(8), 2369; https://doi.org/10.3390/ijms19082369

Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome

1
Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki 852-8501, Japan
2
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Kubara 2-1001-1, Omura 856-8562, Japan
*
Author to whom correspondence should be addressed.
Received: 12 July 2018 / Revised: 8 August 2018 / Accepted: 10 August 2018 / Published: 11 August 2018
(This article belongs to the Special Issue Mechanisms of Disease in Sjögren Syndrome)
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Abstract

The pathogenesis of Sjögren’s syndrome (SS) involves multiple factors including genetic background, cell death, and exocrine dysfunction. We here discuss apoptotic control in exocrine glands in SS by showing various pro- and anti-apoptotic pathways. Although the membrane-bound and soluble form of the Fas/Fas ligand system is a leading player with activation of the death domain and caspase 8/3 cleavage, the role of soluble Fas/FasL (including its polymorphism) in apoptosis is controversial. The tumor necrosis factor related apoptosis-inducing ligand (TRAIL)-mediated apoptosis of salivary gland epithelial cells (SGECs) involves a mitochondrial pathway that includes caspase 9 cleavage. The involvement of innate immunity cells such as toll-like receptors (TLRs) has been investigated; TLR2-4 and TLR7-9 are associated with the induction of inflammation in exocrine glands of SS patients. TLR3 has the potential to induce the apoptosis of SS patients’ SGECs. Linkage of epidermal growth factor (EGF) was shown in exocrine glands in SS, and it inhibited the Fas/FasL system with the help of cell-survival factors. TLR3 has dual actions to cause inflammation as well as apoptosis, which are inhibited by EGF. In conclusion, apoptosis in exocrine glands of SS patients is tightly controlled by balance of pro-apoptotic signals and growth factor. View Full-Text
Keywords: Sjögren’s syndrome; apoptosis; Fas; TLR; EGF; salivary gland epithelial cells; cell survival molecule Sjögren’s syndrome; apoptosis; Fas; TLR; EGF; salivary gland epithelial cells; cell survival molecule
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Nakamura, H.; Horai, Y.; Shimizu, T.; Kawakami, A. Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome. Int. J. Mol. Sci. 2018, 19, 2369.

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