Sulforaphane attenuates dextran sodium sulphate induced intestinal inflammation via IL-10/STAT3 signaling mediated macrophage phenotype switching
Sulforaphane attenuates dextran sodium sulphate induced intestinal inflammation via IL-10/STAT3 signaling mediated macrophage phenotype switching
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DOI：
10.1016/j.fshw.2021.07.014
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发表时间：
2022-01
影响因子：
7
通讯作者：
Yuyang Sun;Jiqing Tang;Cui Li;Jun Liu;Haijie Liu
中科院分区：
文献类型：
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作者：
Yuyang Sun;Jiqing Tang;Cui Li;Jun Liu;Haijie Liu
先天免疫，特别是巨噬细胞，对肠道内稳态至关重要。萝卜硫素是一种从十字花科蔬菜中提取的膳食异硫氰酸盐，据报道可以预防肠道炎症。然而，巨噬细胞在萝卜硫素介导的肠道炎症中的作用及其潜在的分子机制尚未得到研究。在本研究中，萝卜硫素能有效减轻右旋糖酐硫酸钠（DSS）引起的小鼠肠道炎症。值得注意的是，在肠和骨髓源性巨噬细胞（bmdm）中，萝卜硫素扭曲了从经典（M1）激活表型到替代（M2）激活表型的转换。DSS或脂多糖(LPS) +干扰素γ(IFN-γ)诱导的M1相关maker基因表达水平被萝卜硫素抑制，而M2标记基因表达水平被提高。这导致炎症介质的改变，特别是白细胞介素-10 (IL-10)，在结肠组织和bmdm培养基中都是如此。随后，IL-10被发现通过激活STAT3信号通路介导萝卜硫素诱导的bmms M2表型转换。免疫荧光分析证实了这一点，结肠切片中p- stat3阳性细胞数量增加。此外，抗il -10中和抗体显著干扰萝卜硫素诱导bmms的M2表型，降低STAT3磷酸化。本研究结果介绍了萝卜硫素在以巨噬细胞为治疗靶点的肠道炎症治疗中的潜在应用。
Innate immunity, particularly macrophages, is critical for intestinal homeostasis. Sulforaphane, a dietary isothiocyanate from cruciferous vegetables, has been reported to protect against intestinal inflammation. However, the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet. In this study, sulforaphane effectively attenuated dextran sodium sulphate (DSS) induced intestinal inflammation in murine model. Of note, sulforaphane skewed the switching from classically (M1) to alternatively (M2) activated phenotype both in intestinal and bone marrow-derived macrophages (BMDMs). The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide (LPS) plus interferon gamma-γ(IFN-γ) were suppressed by sulforaphane while M2 marker gene expression levels were improved. This resulted in alteration of inflammatory mediators, particularly interleukin-10 (IL-10), both in colon tissues and culture medium of BMDMs. Subsequently, IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling. This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections. Moreover, anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation. Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.