The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.
Invest Ophthalmol Vis Sci. 2013 Sep 5;54(9):6012-7. doi: 10.1167/iovs.13-12159.
To investigate the role of Toll-like receptors (TLRs) 2, 3, 4, and 8 in the pathogenesis of Behcet's disease (BD).
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.
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.
A higher expression of TLRs may be involved in the pathogenesis of BD.
探讨 Toll 样受体(TLR)2、3、4 和 8 在白塞病(BD)发病机制中的作用。
本研究纳入 16 例活动期眼型 BD 患者和 16 名健康志愿者。从 PBMC 中提取总 RNA,以确定 TLRs(包括 TLR2、TLR3、TLR4 和 TLR8)的 mRNA 水平。通过 FACS 分析研究这些 TLR 的细胞表面受体活性。用 TLR 配体(如 LPS、PGN、R848 或 PolyI:C)培养患者和对照的单核细胞和幼稚 T 细胞。收集培养上清液,通过 ELISA 分析 IL-17、IL-1β 和 IL-23。
与对照组相比,活动期 BD 患者 TLR2、TLR3、TLR4 和 TLR8 的 mRNA 和蛋白水平表达明显升高。用 LPS 或 PGN 刺激单核细胞后,上清液中检测到的 IL-1β 和 IL-23 水平明显升高。与对照组相比,用 LPS 或 PGN 刺激后,BD 患者的幼稚 T 细胞和单核细胞上清液中 IL-17 水平明显升高。用 R848 或 PolyI:C 刺激后,BD 患者和对照组的幼稚 T 细胞和单核细胞上清液中 IL-17 水平以及单核细胞上清液中 IL-23 水平无差异。
TLRs 的高表达可能与 BD 的发病机制有关。