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  • Artesunate reduces serum lipopolysaccharide in cecal ligation/puncture mice via enhanced LPS internalization by macrophages through increased mRNA expression of scavenger receptors.

Artesunate reduces serum lipopolysaccharide in cecal ligation/puncture mice via enhanced LPS internalization by macrophages through increased mRNA expression of scavenger receptors.

International journal of molecular sciences (2014-01-21)
Bin Li, Mengchen Yu, Xichun Pan, Chuanliang Ren, Wei Peng, Xiaoli Li, Weiwei Jiang, Jiang Zheng, Hong Zhou
ABSTRACT

Innate immunity is the first line of defense in human beings against pathogen infection; monocytes/macrophages are the primary cells of the innate immune system. Recently, macrophages/monocytes have been discovered to participate in LPS clearance, and the clearance efficiency determines the magnitude of the inflammatory response and subsequent organ injury. Previously, we reported that artesunate (AS) protected sepsis mice against heat-killed E. coli challenge. Herein, we further confirmed that AS protected cecal ligation/puncture (CLP) sepsis mice. Its protection on sepsis mice was related to not only reduction of pro-inflammatory cytokines and serum LPS levels but also improvement of liver function. Based on the fact that AS did not directly bind and neutralize LPS, we hypothesized that the reduction of serum LPS level might be related to enhancement of LPS internalization and subsequent detoxification. Our results showed that AS increased FITC-LPS internalization by peritoneal macrophage and liver Kupffer cell, but enhancement of LPS internalization by AS was not related to the clathrin-dependent pathway. However, AS induced mRNA expression of important scavenger receptors (SRs); SR-A and MARCO mRNA expression was upregulated, suggesting that AS enhancement of LPS internalization and inhibition of pro-inflammatory cytokines was related to changes in mRNA expression of SRs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O111:B4, FITC conjugate
Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O55:B5, FITC conjugate