Lipopolysaccharide-Induced Vascular Inflammation Model on Microfluidic Chip.

Ungsig Nam,Jessie S Jeon,Joonha Park,Seunggyu Kim

doi:10.3390/mi11080747

Ungsig Nam, Jessie S Jeon + Show 2 more

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https://doi.org/10.3390/mi11080747

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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.

Highlights

Inflammation, the response to harmful stimuli, is the initiation of the defense mechanism of our body [1]
Inflammation is induced by external stimuli such as molecules containing pathogen-associated molecule pattern (PAMP) [2] from bacterial and viral infection and molecules produced in our body such as oxidized low density lipoprotein [3]
Lipopolysaccharide (LPS), which is a component of the outer membrane of Gram-negative bacteria, induces an inflammatory response in the animal’s body; this is extensively used in models for studying inflammation [8]

Summary

Introduction

Inflammation, the response to harmful stimuli, is the initiation of the defense mechanism of our body [1]. The inflammatory response of blood vessels, or endothelial cells is important in pathogenesis of diseases [4]. Lipopolysaccharide (LPS), which is a component of the outer membrane of Gram-negative bacteria, induces an inflammatory response in the animal’s body; this is extensively used in models for studying inflammation [8]. LPS is associated with several diseases such as liver damage, neurological degeneration, chronic inflammation of the gut, and diabetes [9], and initiates inflammatory response and injury of endothelial lining of blood vessels, or endothelial cells [10]. It is important to understand how blood vessels respond to LPS

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