Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS

Abstract Itaconic acid is produced by immune responsive gene 1 (IRG1)-coded enzyme in activated macrophages and known to play an important role in metabolism and immunity. In this study, mechanism of itaconic acid functioning as an anti-inflammatory metabolite was investigated with molecular biology...

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Autores principales:	Xiaoyang Zhu, Yangyang Guo, Zhigang Liu, Jingyi Yang, Huiru Tang, Yulan Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/959d8c87bc274311acd4d3ae86aa21eb
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spelling	oai:doaj.org-article:959d8c87bc274311acd4d3ae86aa21eb2021-12-02T18:50:03ZItaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS10.1038/s41598-021-97352-x2045-2322https://doaj.org/article/959d8c87bc274311acd4d3ae86aa21eb2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97352-xhttps://doaj.org/toc/2045-2322Abstract Itaconic acid is produced by immune responsive gene 1 (IRG1)-coded enzyme in activated macrophages and known to play an important role in metabolism and immunity. In this study, mechanism of itaconic acid functioning as an anti-inflammatory metabolite was investigated with molecular biology and immunology techniques, by employing IRG1-null (prepared with CRISPR) and wild-type macrophages. Experimental results showed that itaconic acid significantly promoted the pentose phosphate pathway (PPP), which subsequently led to significantly higher NADPH oxidase activity and more reactive oxygen species (ROS) production. ROS production increased the expression of anti-inflammatory gene A20, which in turn decreased the production of inflammatory cytokines IL-6, IL-1β and TNF-α. NF-κB, which can up-regulate A20, was also vital in controlling IRG1 and itaconic acid involved immune-modulatory responses in LPS-stimulated macrophage in this study. In addition, itaconic acid inhibited the growth of Salmonella typhimurium in cell through increasing ROS production from NADPH oxidase and the hatching of Schistosoma japonicum eggs in vitro. In short, this study revealed an alternative mechanism by which itaconic acid acts as an anti-inflammatory metabolite and confirmed the inhibition of bacterial pathogens with itaconic acid via ROS in cell. These findings provide the basic knowledge for future biological applications of itaconic acid in anti-inflammation and related pathogens control.Xiaoyang ZhuYangyang GuoZhigang LiuJingyi YangHuiru TangYulan WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaoyang Zhu Yangyang Guo Zhigang Liu Jingyi Yang Huiru Tang Yulan Wang Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
description	Abstract Itaconic acid is produced by immune responsive gene 1 (IRG1)-coded enzyme in activated macrophages and known to play an important role in metabolism and immunity. In this study, mechanism of itaconic acid functioning as an anti-inflammatory metabolite was investigated with molecular biology and immunology techniques, by employing IRG1-null (prepared with CRISPR) and wild-type macrophages. Experimental results showed that itaconic acid significantly promoted the pentose phosphate pathway (PPP), which subsequently led to significantly higher NADPH oxidase activity and more reactive oxygen species (ROS) production. ROS production increased the expression of anti-inflammatory gene A20, which in turn decreased the production of inflammatory cytokines IL-6, IL-1β and TNF-α. NF-κB, which can up-regulate A20, was also vital in controlling IRG1 and itaconic acid involved immune-modulatory responses in LPS-stimulated macrophage in this study. In addition, itaconic acid inhibited the growth of Salmonella typhimurium in cell through increasing ROS production from NADPH oxidase and the hatching of Schistosoma japonicum eggs in vitro. In short, this study revealed an alternative mechanism by which itaconic acid acts as an anti-inflammatory metabolite and confirmed the inhibition of bacterial pathogens with itaconic acid via ROS in cell. These findings provide the basic knowledge for future biological applications of itaconic acid in anti-inflammation and related pathogens control.
format	article
author	Xiaoyang Zhu Yangyang Guo Zhigang Liu Jingyi Yang Huiru Tang Yulan Wang
author_facet	Xiaoyang Zhu Yangyang Guo Zhigang Liu Jingyi Yang Huiru Tang Yulan Wang
author_sort	Xiaoyang Zhu
title	Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
title_short	Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
title_full	Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
title_fullStr	Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
title_full_unstemmed	Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
title_sort	itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ros
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/959d8c87bc274311acd4d3ae86aa21eb
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Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS

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