Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy of Agricultural Sciences, Lanzhou, China.
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
Reprod Domest Anim. 2022 Dec;57(12):1602-1614. doi: 10.1111/rda.14237. Epub 2022 Sep 5.
Melatonin has known anti-inflammatory effects. Yet, how melatonin protects sheep endometrial epithelial cells from inflammation remains unknown. In this study, we investigated the melatonin synthetase AANAT and HIOMT and melatonin membrane receptors MT1 and MT2 distribution in sheep uterus. Using lipopolysaccharide (LPS)-stimulated sheep endometrial epithelial cells as an in vitro inflammation model. The results showed that melatonin attenuated the expression of inflammatory factors in a concentration-response manner. Melatonin also inhibited the LPS-stimulated phosphorylation of ERK1/2, JNK and NF-κB p65. This attenuation was partially blocked by luzindole (a non-specific MT1 and MT2 inhibitor) or 4P-PDOT (specific MT2 inhibitor). In addition, the above inhibition of melatonin was abolished by the PI3K/AKT pathway inhibitor LY294002. It was concluded that melatonin had an inhibitory effect on LPS-induced endometrial epithelial cell inflammation in sheep, which was mediated by the activation of the PI3K/AKT pathway via melatonin receptors.
褪黑素具有已知的抗炎作用。然而，褪黑素如何保护绵羊子宫内膜上皮细胞免受炎症仍不清楚。在这项研究中，我们研究了绵羊子宫中褪黑素合成酶 AANAT 和 HIOMT 以及褪黑素膜受体 MT1 和 MT2 的分布。使用脂多糖（LPS）刺激的绵羊子宫内膜上皮细胞作为体外炎症模型。结果表明，褪黑素以浓度反应方式减弱了炎症因子的表达。褪黑素还抑制了 LPS 刺激的 ERK1/2、JNK 和 NF-κB p65 的磷酸化。这种衰减部分被 luzindole（非特异性 MT1 和 MT2 抑制剂）或 4P-PDOT（特异性 MT2 抑制剂）阻断。此外，PI3K/AKT 通路抑制剂 LY294002 消除了褪黑素的上述抑制作用。结论是，褪黑素对 LPS 诱导的绵羊子宫内膜上皮细胞炎症具有抑制作用，这种作用是通过褪黑素受体通过激活 PI3K/AKT 通路介导的。
