Lipopolysaccharide-Induced Vascular Inflammation Model on Microfluidic Chip

Abstract

Inflammation is the initiation of defense of our body against harmful stimuli. Lipopolysaccharide (LPS), originating from outer membrane of Gram-negative bacteria, causes inflammation in the animal’s body and can develop several diseases. In order to study the inflammatory response to LPS of blood vessels in vitro, 2D models have been mainly used previously. In this study, a microfluidic device was used to investigate independent inflammatory response of endothelial cells by LPS and interaction of inflamed blood vessel with monocytic THP-1 cells. Firstly, the diffusion of LPS across the collagen gel into blood vessel was simulated using COMSOL. Then, inflammatory response to LPS in engineered blood vessel was confirmed by the expression of Intercellular Adhesion Molecule 1 (ICAM-1) and VE-cadherin of blood vessel, and THP-1 cell adhesion and migration assay. Upregulation of ICAM-1 and downregulation of VE-cadherin in an LPS-treated condition was observed compared to normal condition. In the THP-1 cell adhesion and migration assay, the number of adhered and trans-endothelial migrated THP-1 cells were not different between conditions. However, migration distance of THP-1 was longer in the LPS treatment condition. In conclusion, we recapitulated the inflammatory response of blood vessels and the interaction of THP-1 cells with blood vessels due to the diffusion of LPS.