Melatonin protects against lipopolysaccharide-induced epididymitis in sheep epididymal epithelial cells in vitro
Melatonin protects against lipopolysaccharide-induced epididymitis in sheep epididymal epithelial cells in vitro
复制标题
褪黑激素体外保护绵羊附睾上皮细胞免受脂多糖诱导的附睾炎
DOI：
10.1016/j.imlet.2019.09.001
复制
发表时间：
2019-10-01
影响因子：
4.4
通讯作者：
Zhao, Xing-xu
中科院分区：
文献类型：
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作者：
Ge, Wen-bo;Xiao, Long-fei;Zhao, Xing-xu
褪黑激素对炎症有保护作用，但其在附睾炎中的作用尚不清楚。我们在本研究中使用脂多糖（LPS）刺激的羊附睾上皮细胞作为体外炎症模型解决了这一问题。我们发现，白细胞介素（IL）-1 β，IL-6，肿瘤坏死因子α，和环氧合酶（考克斯）-2 mRNA水平;考克斯-2和Toll样受体（TLR）-4蛋白水平;和核因子（NF）-κ B B p65磷酸化增加LPS治疗。褪黑素（10（-11）-10（-7）M）以剂量依赖性方式逆转这些作用。定量逆转录PCR和免疫荧光分析表明，褪黑激素受体MT 1和MT 2在绵羊附睾上皮细胞中表达。褪黑激素对炎症的抑制作用被MT 1和MT 2受体拮抗剂luzindole和MT 2配体4-苯基-2-丙酰胺四醛废除。因此，褪黑素通过抑制TLR 4/NF-κ B信号通路在附睾上皮细胞中发挥抗炎作用，表明其作为治疗绵羊附睾炎的有效药物的潜力。
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)-1 beta, IL-6, tumor necrosis factor alpha, and cyclooxygenase (COX)-2 mRNA levels; COX-2 and Toll-like receptor (TLR)-4 protein levels; and nuclear factor (NF)-kappa B p65 phosphorylation were increased by LPS treatment. These effects were reversed in a dose-dependent manner by melatonin (10(-11)-10(-7) 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-kappa B signaling, suggesting its potential as an effective drug for the treatment of epididymitis in sheep.