College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
Immunol Lett. 2019 Oct;214:45-51. doi: 10.1016/j.imlet.2019.09.001. Epub 2019 Sep 3.
Melatonin has protective effects against inflammation but its role in epididymitis is unknown. We addressed this in the present study using lipopolysaccharide (LPS)-stimulated sheep epididymal epithelial cells as an in vitro inflammation model. We found that interleukin (IL)-1β, IL-6, tumor necrosis factor α, and cyclooxygenase (COX)-2 mRNA levels; COX-2 and Toll-like receptor (TLR)-4 protein levels; and nuclear factor (NF)-κB p65 phosphorylation were increased by LPS treatment. These effects were reversed in a dose-dependent manner by melatonin (10-10 M). Quantitative reverse transcription PCR and immunofluorescence analyses showed that the melatonin receptors MT1 and MT2 were expressed in sheep epididymal epithelial cells. The inhibitory effect of melatonin on inflammation was abrogated by the MT1 and MT2 receptor antagonist luzindole and the MT2 ligand 4-phenyl-2-propanamide tetraldehyde. Thus, melatonin exerted anti-inflammatory effect in epididymal epithelial cells by inhibiting TLR4/NF-κB signaling, suggesting its potential as an effective drug for the treatment of epididymitis in sheep.
褪黑素具有抗炎作用，但它在附睾炎中的作用尚不清楚。本研究采用脂多糖（LPS）刺激的绵羊附睾上皮细胞作为体外炎症模型，探讨了这一问题。结果发现，LPS 处理可使白细胞介素（IL）-1β、IL-6、肿瘤坏死因子 α 和环氧化酶（COX）-2mRNA 水平、COX-2 和 Toll 样受体（TLR）-4 蛋白水平以及核因子（NF）-κB p65 磷酸化增加，而褪黑素（10-10 M）可呈剂量依赖性地逆转这些效应。定量逆转录 PCR 和免疫荧光分析表明，褪黑素受体 MT1 和 MT2 在绵羊附睾上皮细胞中表达。褪黑素对炎症的抑制作用被 MT1 和 MT2 受体拮抗剂 luzindole 和 MT2 配体 4-苯基-2-丙酰胺四醛所阻断。因此，褪黑素通过抑制 TLR4/NF-κB 信号通路发挥附睾上皮细胞抗炎作用，提示其有作为绵羊附睾炎有效治疗药物的潜力。
