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Title: Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
Authors: Zhu, Xiaoyang
Guo, Yangyang
Liu, Zhigang
Yang, Jingyi
Tang, Huiru
Wang, Yulan
Keywords: Science::Medicine
Issue Date: 2021
Source: Zhu, X., Guo, Y., Liu, Z., Yang, J., Tang, H. & Wang, Y. (2021). Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS. Scientific Reports, 11(1), 18173-.
Journal: Scientific Reports
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.
ISSN: 2045-2322
DOI: 10.1038/s41598-021-97352-x
Rights: © 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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