Expression of TNF-related apoptosis inducing ligand (TRAIL) on infiltrating cells and of TRAIL receptors on salivary glands in patients with Sjögren's syndrome

Clin Exp Rheumatol. Nov-Dec 2002;20(6):791-8.


Background: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal non-transformed tissues is unknown.

Objective: To evaluate the role of apoptosis mediated by TRAIL and TRAIL-receptor (TRAIL-R) system in lymphocytic sialadenitis in patients with Sjögren's syndrome.

Methods: The expression of TRAIL and TRAIL-R1, 2, 3 and 4 in lymphocytic sialadenitis was examined by immunoperoxidase staining in patients with Sjögren's syndrome and in normal subjects. To elucidate the mechanism of de novo expression of TRAIL-R1 antigen, we quantitatively investigated its induction by cytokines in human salivary duct cell line (HSG) by cell enzyme-linked immunosorbent assay. In human salivary duct cells stimulated by cytokines, we investigated the induction of apoptotic cell death by recombinant TRAIL protein.

Results: In patients with massive mononuclear cell infiltration, some infiltrating cells showed TRAIL. In patients with severe lymphocytic sialadenitis, TRAIL-R1, TRAIL-R2, or both were strongly expressed on the ductal epithelial cells. Neither TRAIL-R3 nor R4 were observed on ductal epithelium. In contrast, TRAIL-R1 and R2 were not found in the minor salivary glands of normal subjects or patients with mild lymphocytic sialadenitis. Unstimulated HSG cells did not express TRAIL-R1. Interferon-gamma (IFN-gamma) consistently upregulated levels of TRAIL-R1. In contrast, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1 beta), IL-2, and IL-4 had no effect on TRAIL-R1 levels. HSG cells expressing TRAIL-R1 in response to IFN-gamma were susceptible to apoptosis by recombinant TRAIL protein.

Conclusion: Our findings suggest that TRAIL and TRAIL-R system may play a role in the pathogenesis of lymphocytic sialadenitis in patients with Sjögren's syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins
  • Apoptosis* / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunoenzyme Techniques
  • Interferon-gamma / pharmacology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / pharmacology
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Recombinant Proteins / pharmacology
  • Salivary Glands, Minor / metabolism*
  • Salivary Glands, Minor / pathology
  • Sialadenitis / etiology
  • Sialadenitis / metabolism*
  • Sialadenitis / pathology
  • Sjogren's Syndrome / complications
  • Sjogren's Syndrome / metabolism*
  • Sjogren's Syndrome / pathology
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma