WTAP mediates the anti-inflammatory effect of Astragalus mongholicus polysaccharide on THP-1 macrophages.
WTAP mediates the anti-inflammatory effect of Astragalus mongholicus polysaccharide on THP-1 macrophages.
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WTAP介导黄芪多糖对THP-1巨噬细胞的抗炎作用
DOI：
10.3389/fphar.2022.1023878
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
背景：黄芪多糖（黄芪多糖）具有抗炎、抗氧化和免疫调节作用。最近的研究表明n6 -甲基腺苷（m6A）在炎症发生中的表观遗传调控。然而，APS对m6A改性的影响尚不清楚。本研究首次探讨了m6A修饰在APS调控THP-1巨噬细胞炎症中的作用机制。方法：采用不同浓度、不同时间的APS处理lps诱导的THP-1巨噬细胞，分别采用实时荧光定量PCR （qRT-PCR）和western blot检测IL-6 mRNA和蛋白水平。采用m6A定量试剂盒检测m6A修饰水平。western blot法筛选调控m6A修饰的蛋白。在aps处理的THP-1巨噬细胞中，Wilms ' tumor 1- associated protein （WTAP）过表达，检测m6A修饰水平和IL-6表达。结果：证实黄芪多糖可显著降低lps诱导的THP-1巨噬细胞中IL-6水平。同时，APS降低THP-1巨噬细胞中m6A修饰水平和WTAP基因表达。进一步过表达WTAP可显著逆转aps诱导的m6A修饰水平和IL-6表达。在机制上，APS通过wtap介导的p65核易位调节IL-6的表达。结论：本研究提示WTAP通过调节THP-1巨噬细胞中m6A修饰水平介导黄芪多糖的抗炎作用。本研究揭示了APS在表观遗传水平上调控炎症的新维度。
Background: Astragalus mongholicus polysaccharides (APS) have anti-inflammatory, antioxidant and immunomodulatory effects. Recent studies have demonstrated the epigenetic regulation of N6-methyladenosine (m6A) in the development of inflammation. However, the effect of APS on m6A modification is unclear. Here, for the first time, we investigate the mechanism of m6A modification in APS regulation of THP-1 macrophage inflammation. Methods: We treated LPS-induced THP-1 macrophages with APS at different concentrations and times, and detected IL-6 mRNA and protein levels by quantitative real-time PCR (qRT-PCR) and western blot, respectively. The m6A modification level was detected by m6A quantification kit. The proteins that regulate m6A modification were screened by western blot. Wilms’ tumor 1-associating protein (WTAP) was overexpressed in APS-treated THP-1 macrophages and the m6A modification level and IL-6 expressions were detected. Results: These findings confirmed that APS significantly abolished LPS-induced IL-6 levels in THP-1 macrophages. Meanwhile, APS reduced m6A modification levels and WTAP gene expression in THP-1 macrophages. Further overexpression of WTAP can significantly reverse APS-induced m6A modification level and IL-6 expression. Mechanistically, APS regulates IL-6 expression through WTAP-mediated p65 nuclear translocation. Conclusion: Overall, our study suggested that WTAP mediates the anti-inflammatory effect of APS by regulating m6A modification levels in THP-1 macrophages. This study reveals a new dimension of APS regulation of inflammation at the epigenetic level.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
20.1
作者：
Tabas I;Bornfeldt KE
通讯作者：
Bornfeldt KE
影响因子：
5.7
作者：
Liao, Chien-Huang;Yong, Chen-Yin;Yao, Chih-Jung
通讯作者：
Yao, Chih-Jung
影响因子：
4.3
作者：
Yuan, Yuan;Sun, Mei;Li, Ke-Shen
通讯作者：
Li, Ke-Shen
影响因子：
7.3
作者：
通讯作者：
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