4-Octyl itaconate inhibits poly(I:C)-induced interferon-β secretion in mouse bone marrow-derived macrophages partially by activating Nrf2
Ying-Xing Yue,
Bing-Bing Jia,
Ji-Rong Wang,
Ying-Zheng Weng,
Gen-Xiang Mao,
Yan Lu,
Jing Yan,
Zhou-Xin Yang
Affiliations
Ying-Xing Yue
Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Bing-Bing Jia
Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Ji-Rong Wang
Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Ying-Zheng Weng
Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Gen-Xiang Mao
Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Yan Lu
Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Jing Yan
Corresponding author.; Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Zhou-Xin Yang
Corresponding author.; Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, 1229 Gudun Road, Hangzhou, China
Viruses have become a major threat to human health. Interferon-β (IFN-β) has a key role in the antivirus process, as it can increase the expression of antivirus-associated genes. Itaconate and its derivatives can regulate the immune response, secretion of inflammatory factors, and pyroptosis of macrophages. The effect of itaconate on IFN-β secretion of double-stranded RNA-induced macrophages are not well known. A derivative of itaconate, 4-octoyl itaconate (4-OI), was used to treat mouse bone marrow-derived macrophages (BMDM) induced with 100 μg/mL poly(I:C). The IFN-β concentration was detected through ELISA, and IFN-β mRNA expression was detected through quantitative PCR. High-throughput transcriptome sequencing was used to analyze changes in the BMDM transcriptome after 4-OI treatment. The Nrf2 expression was knocked down with siRNA.4-OI inhibited poly(I:C)-induced IFN-β secretion and mRNA expression in BMDM. Results of transcriptome sequencing revealed that 4-OI downregulated 1047 genes and upregulated 822 genes. GO and KEGG enrichment of differently expressed genes revealed that many downregulated genes were related to the anti-virus process, whereas many upregulated genes were related to metabolism. The Nrf2 inhibitor ML385 and Nrf2 siRNA could partially reverse the inhibitory effect of 4-OI. In conclusion, 4-octyl itaconate could inhibit the poly(I:C)-induced interferon-β secretion in BMDM partially by regulating Nrf2.
