Interleukin-9 deficiency affects lipopolysaccharide-induced macrophage-related oxidative stress and myocardial cell apoptosis via the Nrf2 pathway both in vivo and in vitro
Interleukin-9 deficiency affects lipopolysaccharide-induced macrophage-related oxidative stress and myocardial cell apoptosis via the Nrf2 pathway both in vivo and in vitro
复制标题
Interleukin-9 缺乏通过 Nrf2 通路影响体内和体外脂多糖诱导的巨噬细胞相关氧化应激和心肌细胞凋亡
DOI：
10.1002/biof.1754
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发表时间：
2021-05-12
期刊：
影响因子：
6
通讯作者：
Liu, Ling
中科院分区：
文献类型：
--
作者：
Liang, Zhishan;Pan, Fuze;Liu, Ling
此前的研究表明，白介素9（IL-9）与心血管疾病有关，包括高血压和心脏纤维化。本研究旨在探讨IL-9在脂多糖（LPS）诱导的心肌细胞（MC）凋亡中的作用。用LPS处理小鼠，并测量IL-9表达，结果显示，与WT小鼠相比，LPS处理的小鼠心脏Mo源性IL-9增加。此外，还评估了IL-9缺乏（IL-9-/-）对巨噬细胞（Mo）相关的氧化应激和MC凋亡的影响，结果显示，IL-9敲除显着加剧LPS处理小鼠的心功能障碍，抑制Nrf2核转移，促进M1和M2 Mos失衡，加剧氧化应激和MC凋亡。 ML385（一种特定的核因子红细胞 2 相关因子 2 (Nrf2) 通路抑制剂）治疗可显着减轻 LPS 治疗的 IL-9-/- 小鼠的上述影响。用LPS处理来自野生型（WT）小鼠和IL-9-/-小鼠的骨髓来源的Mos，并测量Mos的分化和氧化应激水平。还在体外分析了 Mo 分化对小鼠 MC 凋亡的影响。结果表明，LPS 诱导的 M1 Mo/M2 Mo 失衡和 Mo 相关的氧化应激通过 IL-9 敲除得到缓解，但通过 ML385 治疗加剧。 IL-9 缺乏对 LPS 处理的 Mos 介导的 MC 凋亡的保护作用被 ML-385 逆转。我们的结果表明，IL-9的缺失降低了Mos中Nrf2的核转位，从而进一步加剧了Mo相关的氧化应激和MC凋亡。 IL-9 可能是预防 LPS 引起的心脏损伤的靶点。
Previous studies showed that interleukin-9 (IL-9) is involved in cardiovascular diseases, including hypertension and cardiac fibrosis. This study aimed to investigate the role of IL-9 in lipopolysaccharide (LPS)-induced myocardial cell (MC) apoptosis. Mice were treated with LPS, and IL-9 expression was measured and the results showed that compared with WT mice, LPS-treated mice exhibited increased cardiac Mo-derived IL-9. Additionally, the effects of IL-9 deficiency (IL-9-/-) on macrophage (Mo)-related oxidative stress and MC apoptosis were evaluated, the results showed that IL-9 knockout significantly exacerbated cardiac dysfunction, inhibited Nrf2 nuclear transfer, promoted an imbalance in M1 and M2 Mos, and exacerbated oxidative stress and MC apoptosis in LPS-treated mice. Treatment with ML385, a specific nuclear factor erythroid-2 related factor 2 (Nrf2) pathway inhibitor significantly alleviated the above effects in LPS-treated IL-9-/- mice. Bone marrow-derived Mos from wild-type (WT) mice and IL-9-/- mice were treated with LPS, and the differentiation and oxidative stress levels of Mos were measured. The effect of Mo differentiation on mouse MC apoptosis was also analyzed in vitro. The results showed that LPS-induced M1 Mo/M2 Mo imbalance and Mo-related oxidative stress were alleviated by IL-9 knockout but were exacerbated by ML385 treatment. The protective effects of IL-9 deficiency on the MC apoptosis mediated by LPS-treated Mos were reversed by ML-385. Our results suggest that deletion of IL-9 decreased the nuclear translocation of Nrf2 in Mos, which further aggravated Mo-related oxidative stress and MC apoptosis. IL-9 may be a target for the prevention of LPS-induced cardiac injury.