Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
J Endocrinol. 2012 Aug;214(2):145-53. doi: 10.1530/JOE-12-0147. Epub 2012 May 22.
Matrix metalloproteinases (MMPs) have been involved in inflammatory and degradative processes in pathologic conditions. The purpose of this study was to investigate the protective effect of melatonin in human umbilical vein endothelial cell (HUVEC) monolayer permeability and the regulation of MMP9 induced by interleukin 1β (IL1β (IL1B)) in HUVECs. Protection studies were carried out with melatonin, a well-known antioxidant and antiinflammatory molecule. MMP9 expression was increased with IL1β induction in HUVECs. Melatonin showed a barrier-protective role by downregulation of MMP9 and upregulation of tissue inhibitor of metalloproteinase-1 expression in HUVECs. Meanwhile, melatonin also decreased sodium fluorescein permeability and counteracted the downregulation of vascular endothelial cadherin and occludin expression in HUVECs. During inflammatory stimulus, nuclear factor-κB (NF-κB) plays a significant role in regulating MMP genes expression, thus the function of NF-κB in HUVECs' barrier disruption was investigated. IL1β induced nuclear translocation of NF-κB in HUVECs and regulated MMP9 expression. However, NF-κB translocation into the nucleus was inhibited significantly by melatonin. Our results show that melatonin decreases the permeability of monolayer endothelial cell induced by IL1β. At the same time, melatonin decreased the expression and activity of MMP9 by a NF-κB-dependent pathway in HUVECs induced by IL1β.
基质金属蛋白酶（MMPs）参与了病理条件下的炎症和降解过程。本研究旨在探讨褪黑素对人脐静脉内皮细胞（HUVEC）单层通透性的保护作用，以及褪黑素对白细胞介素 1β（IL1β）诱导的 HUVEC 中 MMP9 的调节作用。采用褪黑素作为一种已知的抗氧化和抗炎分子进行保护研究。MMP9 的表达在 HUVEC 中随着 IL1β 的诱导而增加。褪黑素通过下调 MMP9 和上调组织金属蛋白酶抑制剂-1 的表达，在 HUVEC 中发挥屏障保护作用。同时，褪黑素还降低了钠荧光素的通透性，并抵消了 HUVEC 中血管内皮钙黏蛋白和闭合蛋白表达的下调。在炎症刺激过程中，核因子-κB（NF-κB）在调节 MMP 基因表达方面起着重要作用，因此研究了 NF-κB 在 HUVEC 屏障破坏中的作用。IL1β 诱导 NF-κB 在 HUVEC 中的核转位，并调节 MMP9 的表达。然而，NF-κB 向核内的转位被褪黑素显著抑制。我们的结果表明，褪黑素可降低 IL1β 诱导的单层内皮细胞通透性。同时，褪黑素通过 NF-κB 依赖性途径降低了 IL1β 诱导的 HUVEC 中 MMP9 的表达和活性。
