Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress.
Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress.
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衣康酸二甲酯通过氧化应激减轻巨噬细胞焦亡
DOI：
10.1186/s12865-021-00463-3
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发表时间：
2021-11-08
期刊：
影响因子：
3
通讯作者：
Yang ZX
中科院分区：
文献类型：
--
作者：
Huang SS;Guo DY;Jia BB;Cai GL;Yan J;Lu Y;Yang ZX
巨噬细胞作为先天免疫系统的关键细胞参与许多疾病的病理生理学。焦亡是巨噬细胞死亡的一种形式，它诱导巨噬细胞中吞噬物质的胞质分裂，从而防御感染。衣康酸二甲酯 (DI) 是衣康酸的类似物，具有抗炎作用。然而，衣康酸二甲酯对巨噬细胞焦亡的影响尚未明确阐明。因此，本研究旨在分析DI治疗对巨噬细胞焦亡模型（脂多糖，LPS + 三磷酸腺苷，ATP）的影响。结果表明，0.25 mM DI 可改善巨噬细胞焦亡并下调白介素 (IL)-1β 表达。然后，使用实时定量聚合酶链反应（RT-qPCR）确认上调的氧化应激相关基因（GclcandGss）和下调的炎症相关基因（IL-12β和IL-1β）的RNA测序结果。此外，基因本体（GO）富集分析表明差异基因与转录水平和DNA复制相关。京都基因和基因组百科全书 (KEGG) 富集显示，肿瘤坏死因子 (TNF)、Jak、Toll 样受体和 IL-17 等信号通路在 DI 治疗后发生了改变。 N-乙酰-L-半胱氨酸（NAC）逆转了DI对LPS + ATP诱导的巨噬细胞焦亡的影响，并上调IL-1β的表达。氧化应激相关蛋白 Nrf2 参与巨噬细胞焦亡的 DI 调节。总而言之，这些发现表明 DI 通过氧化应激减轻巨噬细胞的焦亡。
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 (GclcandGss) and downregulated inflammation-related genes (IL-12βandIL-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.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
Itaconate连接琥珀酸脱氢酶与巨噬细胞代谢重塑和调节炎症的联系。
影响因子：
29
作者：
Lampropoulou V;Sergushichev A;Bambouskova M;Nair S;Vincent EE;Loginicheva E;Cervantes-Barragan L;Ma X;Huang SC;Griss T;Weinheimer CJ;Khader S;Randolph GJ;Pearce EJ;Jones RG;Diwan A;Diamond MS;Artyomov MN
通讯作者：
Artyomov MN
影响因子：
29.4
作者：
Pourcet B;Zecchin M;Ferri L;Beauchamp J;Sitaula S;Billon C;Delhaye S;Vanhoutte J;Mayeuf-Louchart A;Thorel Q;Haas JT;Eeckhoute J;Dombrowicz D;Duhem C;Boulinguiez A;Lancel S;Sebti Y;Burris TP;Staels B;Duez HM
通讯作者：
Duez HM
影响因子：
64.8
作者：
Bambouskova M;Gorvel L;Lampropoulou V;Sergushichev A;Loginicheva E;Johnson K;Korenfeld D;Mathyer ME;Kim H;Huang LH;Duncan D;Bregman H;Keskin A;Santeford A;Apte RS;Sehgal R;Johnson B;Amarasinghe GK;Soares MP;Satoh T;Akira S;Hai T;de Guzman Strong C;Auclair K;Roddy TP;Biller SA;Jovanovic M;Klechevsky E;Stewart KM;Randolph GJ;Artyomov MN
通讯作者：
Artyomov MN
影响因子：
9.3
作者：
Kuo, Ping-Chang;Weng, Wen-Tsan;Yen, Jui-Hung
通讯作者：
Yen, Jui-Hung