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

Hideki Nakamura1, Yoshiro Horai2, Toshimasa Shimizu3

  • 1Department 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. nhideki@nagasaki-u.ac.jp.

International Journal of Molecular Sciences
|August 15, 2018
PubMed

Insights

Sjögren's syndrome involves complex apoptotic pathways in exocrine glands. Epidermal growth factor (EGF) and toll-like receptors (TLRs) modulate these cell death processes, influencing inflammation and apoptosis.

Area of Science:

  • Immunology
  • Cell Biology
  • Pathogenesis of Autoimmune Diseases

Background:

  • Sjögren's syndrome (SS) pathogenesis involves genetic, cellular, and exocrine dysfunction factors.
  • Apoptosis, or programmed cell death, plays a critical role in the exocrine gland pathology of SS.

Purpose of the Study:

  • To elucidate the intricate mechanisms of apoptotic control within the exocrine glands of SS patients.
  • To investigate the roles of key molecular pathways, including Fas/Fas ligand, TRAIL, toll-like receptors (TLRs), and epidermal growth factor (EGF), in SS-related apoptosis.

Main Methods:

  • Review and discussion of pro- and anti-apoptotic signaling pathways.
  • Analysis of the Fas/Fas ligand system, including membrane-bound and soluble forms.
  • Investigation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL)-mediated apoptosis via mitochondrial pathways.
  • Examination of toll-like receptor (TLR) involvement in inflammation and apoptosis of salivary gland epithelial cells (SGECs).
  • Assessment of epidermal growth factor (EGF) interactions with apoptotic pathways.

Main Results:

  • The Fas/Fas ligand system is implicated in apoptosis, though its soluble form's role is debated.
  • TRAIL induces apoptosis in SGECs through a mitochondrial pathway involving caspase 9.
  • TLRs (2-4, 7-9) are linked to inflammation, while TLR3 can induce SGEC apoptosis.
  • Epidermal growth factor (EGF) inhibits the Fas/FasL system and possesses dual actions on TLR3-induced inflammation and apoptosis.

Conclusions:

  • Apoptosis in SS exocrine glands is a tightly regulated process.
  • The balance between pro-apoptotic signals and growth factors like EGF is crucial in controlling SS pathogenesis.
  • Understanding these pathways offers potential therapeutic targets for Sjögren's syndrome.
Keywords:
EGFFasSjögren’s syndromeTLRapoptosiscell survival moleculesalivary gland epithelial cells

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