Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome
AbstractThe 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
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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.
Nakamura H, Horai Y, Shimizu T, Kawakami A. Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome. International Journal of Molecular Sciences. 2018; 19(8):2369.Chicago/Turabian Style
Nakamura, Hideki; Horai, Yoshiro; Shimizu, Toshimasa; Kawakami, Atsushi. 2018. "Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome." Int. J. Mol. Sci. 19, no. 8: 2369.
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