4.6 Article

Higher Expression of Toll-like Receptors 2, 3, 4, and 8 in Ocular Behcet's Disease

Journal

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 54, Issue 9, Pages 6012-6017

Publisher

ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.13-12159

Keywords

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

Categories

Funding

  1. National Natural Science Foundation [30973242]
  2. Natural Science Foundation [81130019]
  3. Clinic Key Project of Ministry of Health, Basic Research Program of Chongqing [cstc2013jcyjC10001]
  4. Chongqing Key Laboratory of Ophthalmology (CSTC) [2008CA5003]
  5. Key Project of Health Bureau of Chongqing [2012-1-003]
  6. Fund for PAR-EU Scholars Program

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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 naive 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-1 beta, 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-1 beta 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 naive 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 naive 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.

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