Higher expression of Toll-like receptors 2, 3, 4, and 8 in ocular Behcet's disease

Invest Ophthalmol Vis Sci. 2013 Sep 5;54(9):6012-7. doi: 10.1167/iovs.13-12159.

Abstract

Purpose: To investigate the role of Toll-like receptors (TLRs) 2, 3, 4, and 8 in the pathogenesis of Behcet's disease (BD).

Methods: Sixteen patients with active ocular BD and 16 healthy volunteers were included in this study. Total RNA was isolated from PBMCs to determine mRNA levels of TLRs, including TLR2, TLR3, TLR4, and TLR8. Cell surface receptor activity of these TLRs was investigated by FACS analysis. Monocytes and naïve T cells from patients and controls were cultured with or without TLR ligands, such as LPS, PGN, R848, or PolyI:C. Culture supernatants were collected and IL-17, IL-1β, and IL-23 were analyzed by ELISA.

Results: A markedly higher expression at the mRNA and protein level of TLR2, TLR3, TLR4, and TLR8 was observed in active BD patients as compared with controls. Significantly higher levels of IL-1β and IL-23 were detected in the supernatants of monocytes stimulated with LPS or PGN. A significantly higher level of IL-17 was observed in the supernatants of naïve T cells and monocytes stimulated with LPS or PGN in BD patients as compared with controls. Upon stimulation with R848 or PolyI:C, the levels of IL-17 in the supernatants of naïve T cells and monocytes and IL-23 levels in the supernatants of monocytes were not different between BD patients and controls.

Conclusions: A higher expression of TLRs may be involved in the pathogenesis of BD.

Keywords: Behcet's disease; IL-17; TLR ligands; Toll-like receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Behcet Syndrome / genetics*
  • Behcet Syndrome / immunology
  • Behcet Syndrome / metabolism
  • Behcet Syndrome / pathology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Gene Expression Regulation*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Male
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 2 / biosynthesis
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 3 / biosynthesis
  • Toll-Like Receptor 3 / genetics*
  • Toll-Like Receptor 4 / biosynthesis
  • Toll-Like Receptor 4 / genetics*

Substances

  • Cytokines
  • RNA, Messenger
  • Toll-Like Receptor 2
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4