Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress

Abstract Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shan-Shan Huang, Dong-Yang Guo, Bing-Bing Jia, Guo-Long Cai, Jing Yan, Yan Lu, Zhou-Xin Yang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Dimethyl itaconate Pyroptosis Macrophages Oxidative stress Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/54f19b449c5f41079bb108ea1fe913b2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:54f19b449c5f41079bb108ea1fe913b2
record_format	dspace
spelling	oai:doaj.org-article:54f19b449c5f41079bb108ea1fe913b22021-11-14T12:08:08ZDimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress10.1186/s12865-021-00463-31471-2172https://doaj.org/article/54f19b449c5f41079bb108ea1fe913b22021-11-01T00:00:00Zhttps://doi.org/10.1186/s12865-021-00463-3https://doaj.org/toc/1471-2172Abstract Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS + Adenosine Triphosphate, ATP). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1β expression. Then, real-time quantitative polymerase chain reaction (RT-qPCR) was used to confirm the result of RNA-sequencing of the upregulated oxidative stress-related genes (Gclc and Gss) and downregulated inflammation-related genes (IL-12β and IL-1β). In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that signaling pathways, such as tumor necrosis factor (TNF), Jak, Toll-like receptor and IL-17, were altered after DI treatment. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS + ATP-induced macrophage pyroptosis and upregulated the IL-1β expression. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress.Shan-Shan HuangDong-Yang GuoBing-Bing JiaGuo-Long CaiJing YanYan LuZhou-Xin YangBMCarticleDimethyl itaconatePyroptosisMacrophagesOxidative stressImmunologic diseases. AllergyRC581-607ENBMC Immunology, Vol 22, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dimethyl itaconate Pyroptosis Macrophages Oxidative stress Immunologic diseases. Allergy RC581-607
spellingShingle	Dimethyl itaconate Pyroptosis Macrophages Oxidative stress Immunologic diseases. Allergy RC581-607 Shan-Shan Huang Dong-Yang Guo Bing-Bing Jia Guo-Long Cai Jing Yan Yan Lu Zhou-Xin Yang Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress
description	Abstract Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS + Adenosine Triphosphate, ATP). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1β expression. Then, real-time quantitative polymerase chain reaction (RT-qPCR) was used to confirm the result of RNA-sequencing of the upregulated oxidative stress-related genes (Gclc and Gss) and downregulated inflammation-related genes (IL-12β and IL-1β). In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that signaling pathways, such as tumor necrosis factor (TNF), Jak, Toll-like receptor and IL-17, were altered after DI treatment. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS + ATP-induced macrophage pyroptosis and upregulated the IL-1β expression. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress.
format	article
author	Shan-Shan Huang Dong-Yang Guo Bing-Bing Jia Guo-Long Cai Jing Yan Yan Lu Zhou-Xin Yang
author_facet	Shan-Shan Huang Dong-Yang Guo Bing-Bing Jia Guo-Long Cai Jing Yan Yan Lu Zhou-Xin Yang
author_sort	Shan-Shan Huang
title	Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress
title_short	Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress
title_full	Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress
title_fullStr	Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress
title_full_unstemmed	Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress
title_sort	dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress
publisher	BMC
publishDate	2021
url	https://doaj.org/article/54f19b449c5f41079bb108ea1fe913b2
work_keys_str_mv	AT shanshanhuang dimethylitaconatealleviatesthepyroptosisofmacrophagesthroughoxidativestress AT dongyangguo dimethylitaconatealleviatesthepyroptosisofmacrophagesthroughoxidativestress AT bingbingjia dimethylitaconatealleviatesthepyroptosisofmacrophagesthroughoxidativestress AT guolongcai dimethylitaconatealleviatesthepyroptosisofmacrophagesthroughoxidativestress AT jingyan dimethylitaconatealleviatesthepyroptosisofmacrophagesthroughoxidativestress AT yanlu dimethylitaconatealleviatesthepyroptosisofmacrophagesthroughoxidativestress AT zhouxinyang dimethylitaconatealleviatesthepyroptosisofmacrophagesthroughoxidativestress
_version_	1718429401880723456

Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress

Ejemplares similares