Interleukin-8 regulates endothelial permeability by down-regulation of tight junction but not dependent on integrins induced focal adhesions

Int J Biol Sci. 2013 Sep 23;9(9):966-79. doi: 10.7150/ijbs.6996. eCollection 2013.

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.

Keywords: Claudin-5; Endothelial permeability; IL-8; Occludin; Tight junction; ZO-1..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Line
  • Claudin-5 / genetics
  • Claudin-5 / metabolism
  • Down-Regulation / drug effects
  • Endothelial Cells / ultrastructure
  • Endothelium / metabolism
  • Endothelium / ultrastructure
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism*
  • Focal Adhesions / ultrastructure
  • Humans
  • Integrins / genetics
  • Integrins / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Interleukin-8 / pharmacology
  • Interleukin-8 / physiology*
  • Occludin / genetics
  • Occludin / metabolism
  • Permeability / drug effects
  • RNA, Messenger / metabolism
  • Tight Junctions / genetics*
  • Tight Junctions / metabolism
  • Tight Junctions / ultrastructure
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Claudin-5
  • Integrins
  • Interleukin-8
  • Occludin
  • RNA, Messenger
  • TJP1 protein, human
  • Zonula Occludens-1 Protein