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http://dx.doi.org/10.14348/molcells.2020.0030

Lysophosphatidylcholine Enhances Bactericidal Activity by Promoting Phagosome Maturation via the Activation of the NF-κB Pathway during Salmonella Infection in Mouse Macrophages  

Lee, Hyo-Ji (Department of Biological Sciences and Institute of Life Sciences, Kangwon National University)
Hong, Wan-Gi (BIT Medical Convergence Graduate Program, Kangwon National University)
Woo, Yunseo (Department of Biological Sciences and Institute of Life Sciences, Kangwon National University)
Ahn, Jae-Hee (Department of Pharmacy, Kangwon National University)
Ko, Hyun-Jeong (Department of Pharmacy, Kangwon National University)
Kim, Hyeran (Department of Biological Sciences and Institute of Life Sciences, Kangwon National University)
Moon, Sungjin (Department of Biological Sciences and Institute of Life Sciences, Kangwon National University)
Hahn, Tae-Wook (Department of Veterinary Medicine, Kangwon National University)
Jung, Young Mee (Department of Chemistry, Kangwon National University)
Song, Dong-Keun (Department of Pharmacology, College of Medicine, Hallym University)
Jung, Yu-Jin (Department of Biological Sciences and Institute of Life Sciences, Kangwon National University)
Publication Information
Molecules and Cells / v.43, no.12, 2020 , pp. 989-1001 More about this Journal
Abstract
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular pathogen that causes salmonellosis and mortality worldwide. S. Typhimurium infects macrophages and survives within phagosomes by avoiding the phagosome-lysosome fusion system. Phagosomes sequentially acquire different Rab GTPases during maturation and eventually fuse with acidic lysosomes. Lysophosphatidylcholine (LPC) is a bioactive lipid that is associated with the generation of chemoattractants and reactive oxygen species (ROS). In our previous study, LPC controlled the intracellular growth of Mycobacterium tuberculosis by promoting phagosome maturation. In this study, to verify whether LPC enhances phagosome maturation and regulates the intracellular growth of S. Typhimurium, macrophages were infected with S. Typhimurium. LPC decreased the intracellular bacterial burden, but it did not induce cytotoxicity in S. Typhimurium-infected cells. In addition, combined administration of LPC and antibiotic significantly reduced the bacterial burden in the spleen and the liver. The ratios of the colocalization of intracellular S. Typhimurium with phagosome maturation markers, such as early endosome antigen 1 (EEA1) and lysosome-associated membrane protein 1 (LAMP-1), were significantly increased in LPC-treated cells. The expression level of cleaved cathepsin D was rapidly increased in LPC-treated cells during S. Typhimurium infection. Treatment with LPC enhanced ROS production, but it did not affect nitric oxide production in S. Typhimurium-infected cells. LPC also rapidly triggered the phosphorylation of IκBα during S. Typhimurium infection. These results suggest that LPC can improve phagosome maturation via ROS-induced activation of NF-κB pathway and thus may be developed as a therapeutic agent to control S. Typhimurium growth.
Keywords
bactericidal activity; lysophosphatidylcholine; macrophage; phagosome maturation; reactive oxygen species; Salmonella Typhimurium;
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