Macrophage-derived sulfur dioxide is a novel inflammation regulator.
Macrophage-derived sulfur dioxide is a novel inflammation regulator.
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DOI：
10.1016/j.bbrc.2020.02.013
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发表时间：
2020-02
影响因子：
3.1
通讯作者：
Zhigang Zhu;Lulu Zhang;Qinghua Chen;Kun Li;Xiaoqi Yu;Chao-shu Tang;W. Kong;Hongfang Jin;Junbao Du;Yaqian Huang
中科院分区：
文献类型：
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作者：
Zhigang Zhu;Lulu Zhang;Qinghua Chen;Kun Li;Xiaoqi Yu;Chao-shu Tang;W. Kong;Hongfang Jin;Junbao Du;Yaqian Huang
Macrophage-mediated inflammation is a key pathophysiological component of cardiovascular diseases, but the underlying mechanisms by which the macrophage regulates inflammation have been unclear. In our study, we, for the first time, showed an endogenous sulfur dioxide (SO2) production in RAW267.4 macrophages by using HPLC and SO2-specific fluorescent probe assays. Moreover, the endogenous SO2generating enzyme aspartate aminotransferase (AAT) was found to be expressed by the macrophages. Furthermore, we showed that AAT2 knockdown triggered spontaneous macrophage-mediated inflammation, as represented by the increased TNF-α and IL-6 levels and the enhanced macrophage chemotaxis; these effects could be reversed by the treatment with a SO2donor. Mechanistically, AAT2 knockdown activated the NF-κB signaling pathway in macrophages, while SO2successfully rescued NF-κB activation. In contrast, forced AAT2 expression reversed AngII-induced NF-κB activation and subsequent macrophage inflammation. Moreover, treatment with a SO2donor also alleviated macrophage infiltration in AngII-treated mouse hearts. Collectively, our data suggest that macrophage-derived SO2is an important regulator of macrophage activation and it acts as an endogenous “on-off switch” in the control of macrophage activation. This knowledge might enable a new therapeutic strategy for cardiovascular diseases.
