Tangeretin attenuates lipopolysaccharide-induced acute lung injury through Notch signaling pathway via suppressing Th17 cell response in mice
Tangeretin attenuates lipopolysaccharide-induced acute lung injury through Notch signaling pathway via suppressing Th17 cell response in mice
复制标题
橘皮素通过抑制小鼠 Th17-细胞反应，通过 Notch 信号通路减轻脂多糖诱导的急性肺损伤
DOI：
10.1016/j.micpath.2019.103826
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发表时间：
2020-01-01
影响因子：
3.8
通讯作者：
Wang, Daoxin
中科院分区：
文献类型：
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作者：
Li, Mengqin;Zhao, Yan;Wang, Daoxin
橘黄素是一种多甲氧基化的黄酮类化合物，在柑橘类水果中含量丰富，已有报道通过抑制核因子-kappaB的激活和促炎细胞因子来抑制炎症。缺口阻断抑制Th17细胞反应，Th17细胞参与急性肺损伤(ALI)的发展。本研究探讨了橘皮素对内毒素诱导的小鼠急性肺损伤的保护作用。雄性C57BL/6小鼠分别给予磷酸盐缓冲液、内毒素、内毒素和橘皮黄素，或内毒素和N-[N-(3，5-difluorophenacetyl)-l-alanyl]-S-phenylglycine叔丁酯(Notch信号抑制剂)，于内毒素攻击后48h处死。用橘黄素或DAPT处理CD4(+)T细胞，72 h后收集，可明显减轻小鼠肺组织病理改变，降低肺湿重/干重比。陈皮素能显著降低肺组织细胞总数、中性粒细胞计数、肺泡灌洗液中肿瘤坏死因子-α含量、肺组织髓过氧化物酶活性。橘皮素能显著降低小鼠肺组织中CD4+IL-17+T细胞百分率和BALF中IL-17、IL-22浓度。与阳性对照(DAPT)一样，橘皮素能抑制Notch信号通路的活性，同时下调酸相关孤儿受体γt和IL-23受体的表达。本研究表明，橘皮黄素通过至少部分抑制Th17反应，通过一种Notch依赖的机制，对脂多糖诱导的ALI具有保护作用。
Tangeretin, a polymethoxylated flavonoid is abundant in citrus fruits, which has been reported to inhibit inflammation by inhibiting NF-kappa B activation and proinflammatory cytokines. Notch blockage inhibits Th17 cells response that are involved in the development of acute lung injury (ALI). This study investigated the protective effects of tangeretin on LPS-induced ALI in mice. Male C57BL/6 mice were treated with phosphate-buffered saline (PBS), lipopolysaccharide (LPS), LPS and tangeretin, or LPS and N- [N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, a Notch signaling inhibitor), which were harvested at 48 h after challenged by LPS. CD4(+) T cells were treated with tangeretin or DAPT and harvested after 72 h. Tangeretin notably attenuated pathological changes and decreased the wet to dry weight ratio of the mouse lungs. The total cell and neutrophil counts, tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid (BALF), myeloperoxidase activity of lung tissue were markedly reduced by tangeretin. The percentage of CD4 + IL-17 + T cells in the lungs and the concentration of interleukin (IL)-17and IL-22 in BALF were significantly down-regulated by tangeretin. As with the positive control (DAPT), tangeretin inhibited the activity of the Notch signaling pathway accompanied with the down-regulation of acid-related orphan receptor gamma t and IL-23 receptor expression. This study demonstrated that tangeretin protects against LPS-induced ALI by suppressing Th17 response at least partially, through a Notch-dependent mechanism.