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.

The impaired intestinal mucosal immune system by valine deficiency for young grass carp (Ctenopharyngodon idella) is associated with decreasing immune status and regulating tight junction proteins transcript abundance in the intestine

“…In Caco-2 cells, studies showed that TNFa down-regulated the expression of ZO-1 [76] and Occludin [77] respectively. Moreover, IL-8 decreased the mRNA level of Occludin, Claudin-5 and ZO-1 in human [78]. In the present study, valine deficiency increased the IL-8 and TNF-a expression in the fish intestine, indicating that valine deficiency down-regulated the expression of Occludin and ZO-1 may be attributed to the upregulation of TNF-a and IL-8 in the intestine for fish.…”

Changes in barrier health status of the gill for grass carp (Ctenopharyngodon idella) during valine deficiency: Regulation of tight junction protein transcript, antioxidant status and apoptosis-related gene expression

“…TNF-a and IL-1b down-regulate the expression of ZO-1 [59] and Occludin [60], respectively, in Caco-2 cells. Moreover, IL-8 decreased Occludin, Claudin-5 and ZO-1 mRNA levels in human vascular endothelial cells [61]. IL-1b, IL-8 and TNF-a expression in the present study increased significantly in valine-limited diet group.…”

Wogonin inhibits LPS-induced vascular permeability via suppressing MLCK/MLC pathway

“…Vascular endothelium is a semipermeable membrane formed by vascular endothelial cell monolayer and localized at the critical interface between the blood and vessel wall [34], which could regulate the exchange balance of dissolved gases, ions and solutes between the inner and outer of vascular endothelium and supply the essential nutrients needed for the normal physiological functions of organs [56]. Vascular hyperpermeability means that it in part lost semipermeable characteristics, which is the hallmark of inflammatory diseases such as atherosclerosis [13] and involved in the development of heart and lung edema, shock and tumor angiogenesis [4].…”