title: Interleukin-8 regulates endothelial permeability by down-regulation of tight junction but not dependent on integrins induced focal adhesions.
abstract: Interleukin-8 (IL-8) is a common inflammatory factor, which involves in various non-specific pathological processes of inflammation. It has been found that increased endothelial permeability accompanied with high expression of IL-8 at site of injured endothelium and atherosclerotic plaque at early stages, suggesting that IL-8 participated in regulating endothelial permeability in the developing processes of vascular disease. The purpose of this study is to investigate the regulation effects of IL-8 on the vascular endothelial permeability, and the mRNA and protein expression of tight junction components (i.e., ZO-1, Claudin-5 and Occludin). Endothelial cells were stimulated by IL-8 with the dose of 50, 100 and 200 ng/mL, and duration of 2, 4, 6, 8h, respectively. The mRNA and protein expression level of tight junction components with IL-8 under different concentration and duration was examined by RT-PCR and Western blot, respectively. Meanwhile, the integrins induced focal adhesions event with IL-8 stimulation was also investigated. The results showed that IL-8 regulated the permeability of endothelium by down-regulation of tight junction in a dose- and time-dependence manner, but was not by integrins induced focal adhesions. This finding reveals the molecular mechanism in the increase of endothelial cell permeability induced by IL-8, which is expected to provide a new idea as a therapeutic target in vascular diseases.
authors.affiliation: Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Hongchi
authors.initials: H
authors.lastname: Yu
authors.forename: Xianliang
authors.initials: X
authors.lastname: Huang
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Xiaoheng
authors.initials: X
authors.lastname: Liu
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000648:ultrastructure; D004727:Endothelium / Q000378:metabolism / Q000648:ultrastructure; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D019108:Tight Junctions / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D062507:Claudin-5; D016023:Integrins; D016209:Interleukin-8; D062793:Occludin; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: Claudin-5; Endothelial permeability; IL-8; Occludin; Tight junction; ZO-1.