Abstract P3141: Human Milk Oligosaccharide Attenuates Lipopolysaccharide-induced Endothelial Hyperpermeability And Migration

Abstract

Background: Endothelial hyperpermeability plays a crucial role in the initial development of vascular inflammation, resulting in endothelial dysfunction. Human milk oligosaccharide (HMO), is the bioactive product, is recognized to protect against obesity and anti-inflammatory activity, but it is unknown what effects and signaling pathways are in endothelial cell (EC) function. Therefore, we examined the hypothesis that the protection of HMO in stabilizing endothelial barrier function as well as improving the cell migration under LPS treatment. Methods and Results: We analyzed the effect of HMO on the permeability and migration of cultured Bovine aortic endothelial cells (BAECs). Our results found that HMO significantly suppressed the expression of phosphorylated ERK1/2 and p38 MAPK but not JNK after exposure to LPS. In addition, immunofluorescence staining revealed that HMOs abolished the nuclear translocation of NF-κB and phosphorylated STAT3, which was accompanied by down-regulation of pro-inflammatory cytokines and chemokines such as TNF-α, IL-1β, MCP-1, VCAM-1, and ICAM-1 under LPS stimulation. Our data demonstrated an improvement of endothelial barrier function as indicated in PECAM-1 endothelial junction as well as an enhancement of cell migration by HMO pre-treatment, followed by LPS treatment. Conclusion: Our results suggest that HMO as a potential therapeutic agent for the reduction of microvascular leakage and inflammation in vascular disease.