Department of Orthopedics, Mingzhou Hospital of Zhejiang University, Ningbo, Zhejiang 315000, P.R. China.
Mol Med Rep. 2019 Oct;20(4):3565-3572. doi: 10.3892/mmr.2019.10631. Epub 2019 Sep 2.
Ankylosing spondylitis (AS) is a common chronic inflammatory autoimmune disease. Toll‑like receptors (TLRs) are involved in non‑specific immunity. In the present study, the roles of TLRs in AS were investigated. The levels of inflammatory cytokines were detected by ELISA and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression levels of TLRs and nuclear factor‑κB (NF‑κB) signaling‑associated factors were determined via RT‑qPCR and western blot analyses. It was observed that the levels of interleukin (IL)‑6, tumor necrosis factor‑α (TNF‑α), C‑reactive protein, TLR4 and TLR5 were increased in patients with AS, whereas those of IL‑10 and TLR3 were decreased. Pomalidomide, a TNF‑α release inhibitor, reduced the expression of IL‑6, TNF‑α, TLR4, TLR5 and phosphorylated‑p65, and upregulated that of IL‑10, TLR3 and p65 in peripheral blood mononuclear cells from patients with AS. Treatment of patients with infliximab, an anti‑TNF‑α monoclonal antibody, induced similar effects in vivo. In conclusion, it was revealed that inhibition of TNF‑α suppressed inflammatory responses in patients with AS, increased the expression of TLR3 and decreased NF‑κB signaling, and the expression of TLR4 and TLR5. The results indicated that TLRs and the NF‑κB signaling pathway were involved in the regulation of inflammatory responses in AS. These findings provided insight into the mechanisms underlying the development of AS and potential novel therapeutic approaches.
强直性脊柱炎（AS）是一种常见的慢性炎症性自身免疫性疾病。Toll 样受体（TLRs）参与非特异性免疫。本研究探讨了 TLRs 在 AS 中的作用。通过 ELISA 和逆转录定量聚合酶链反应（RT-qPCR）检测炎症细胞因子水平。通过 RT-qPCR 和 Western blot 分析测定 TLRs 和核因子-κB（NF-κB）信号相关因子的表达水平。结果观察到，AS 患者的白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）、C 反应蛋白、TLR4 和 TLR5 水平升高，而 IL-10 和 TLR3 水平降低。TNF-α释放抑制剂来那度胺降低了 AS 患者外周血单个核细胞中 IL-6、TNF-α、TLR4、TLR5 和磷酸化-p65 的表达，并上调了 IL-10、TLR3 和 p65 的表达。抗 TNF-α单克隆抗体英夫利昔单抗治疗体内也产生了类似的效果。综上所述，抑制 TNF-α可抑制 AS 患者的炎症反应，增加 TLR3 的表达，降低 NF-κB 信号通路，TLR4 和 TLR5 的表达。结果表明 TLRs 和 NF-κB 信号通路参与了 AS 中炎症反应的调节。这些发现为 AS 的发病机制提供了新的见解，并为潜在的新治疗方法提供了思路。
