Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS + ATP-induced macrophage pyroptosis and upregulated the IL-1β expression. 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. In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. 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). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1β expression. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS + Adenosine Triphosphate, ATP). However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system.

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