title: Melatonin inhibits IL-1β-induced monolayer permeability of human umbilical vein endothelial cells via Rac activation.
abstract: Melatonin is a key factor in the coordination of circadian rhythms and seasonal reproduction. Melatonin and its metabolites directly scavenge free radicals, increase the expression of antioxidant enzymes, and play a role in the anti-inflammatory phase of defense responses. At present, there are no direct data available as to melatonin's possible influence on endothelial cell monolayer permeability, which is a major biological process responsible for vascular diseases. The aim of this study was to investigate the effect of melatonin on IL-1β-induced human umbilical vein endothelial cells (HUVECs) monolayer permeability and then to test the involvement of small GTPase Rac in the melatonin-induced endothelial barrier-protective effects as well as cell contact reorganization. It was found that IL-1β treatment increased the permeability of HUVECs monolayer, disrupted adherens junctions, and down-regulated the expression of VE-cadherin which is the main functional protein of adherens junctions. Melatonin, however, decreased dextran permeability and increased intercellular adherens junction areas reflecting an endothelial cell barrier-protective response. Furthermore, melatonin dramatically improved IL-1β-induced Rac inactivation. Our results show that the barrier-protective effects of melatonin on endothelial cells are mediated by Rac activation and leads to enhancement of adherens junctions.
authors.affiliation: Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Yuan
authors.forename: Bingwei
authors.initials: B
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Xiu
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D000975:Antioxidants; D015820:Cadherins; D053583:Interleukin-1beta; D008550:Melatonin; D020744:rac GTP-Binding Proteins; D000099152:Cadherin 5; C508585:IL1B protein, human