Curcumin Promotes the Expression of IL-35 by Regulating Regulatory T Cell Differentiation and Restrains Uncontrolled Inflammation and Lung Injury in Mice
Curcumin Promotes the Expression of IL-35 by Regulating Regulatory T Cell Differentiation and Restrains Uncontrolled Inflammation and Lung Injury in Mice
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姜黄素通过调节调节性 T 细胞分化促进 IL-35 的表达并抑制小鼠失控的炎症和肺损伤
DOI：
10.1007/s10753-020-01265-2
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发表时间：
2020-06-14
期刊：
影响因子：
5.1
通讯作者：
Xu, Fang
中科院分区：
文献类型：
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作者：
Chen, Yan-qing;Chai, Yu-sen;Xu, Fang
白细胞介素（IL）-35在急性呼吸窘迫综合征（ARDS）/急性肺损伤（ALI）中具有抗炎作用，是相对有前途的药物靶点。研究表明，姜黄素可能在 ALI 中发挥治疗作用，并增强调节性 T 细胞 (Treg) 的抑制功能。为了说明姜黄素对 Treg 细胞分化和 IL-35 表达的调节作用，我们建立了姜黄素预处理的盲肠结扎穿刺（CLP）诱导的急性肺损伤小鼠模型。评估血清中IL-35的表达量、肺损伤严重程度、肺组织中IL-17A、生存率、血清中Treg相关细胞因子水平、肺组织中核因子κB（NF-κB）核转位以及脾CD4+CD25+FOXP3+Treg。此外，还测量了体外幼稚 CD4+ T 细胞分化过程中 Tregs、STAT5 和 IL-35 表达的比例。与CLP组相比，姜黄素预处理(CLP+Cur)组CLP中IL-35表达增加与肺损伤严重程度、肺组织IL-17A蛋白水平和Treg相关细胞因子水平降低一致。用姜黄素预处理，CLP组的存活率攀升至50%，而死亡率为100%。此外，CLP+Cur组中脾脏CD4+CD25+FOXP3+Treg细胞增加。体外，姜黄素处理后，来自幼稚CD4+T细胞的CD4+CD25+FOXP3+Treg细胞、STAT5比例和IL-35表达增加。这些发现表明，姜黄素可能通过激活Treg细胞的分化来调节IL-35，从而控制急性肺损伤中的炎症。
Interleukin (IL)-35, which has an anti-inflammatory role in acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), is relatively promising as a drug target. Studies have shown that curcumin may play a therapeutic role in ALI and enhance the suppressive function of regulatory T cells (Tregs). To illustrate the effect of curcumin on the regulation of Treg cell differentiation and expression of IL-35, we built a cecal ligation and puncture (CLP)–induced acute lung injury mouse mode with curcumin pretreatment. The expression of IL-35 in serum, severity of lung injury, IL-17A in lung tissue, survival rate, Treg-related cytokines levels in serum, nuclear factor-kappa B (NF-κB)’s nuclear translocation in lung tissue, and splenic CD4+CD25+FOXP3+ Tregs were assessed. Furthermore, the proportion of Tregs, STAT5, and IL-35 expression during naïve CD4+ T cell differentiationin vitrowas measured. Compared with the CLP group, the increased IL-35 expression in CLP with the curcumin pretreatment (CLP + Cur) group was consistent with the decreased severity of lung injury, IL-17A protein levels in lung tissue, and Treg-related cytokines levels. Pretreatment with curcumin, the survival rate climbed to 50%, while the mortality rate was 100% in the CLP group. In addition, splenic CD4+CD25+FOXP3+ Treg cells increased in the CLP + Cur group.In vitro, CD4+CD25+FOXP3+ Treg cells from naïve CD4+ T cells, STAT5 proportion, and IL-35 expression increased after curcumin treatment. These findings showed that curcumin might regulate IL-35 by activating the differentiation of Treg cells to control the inflammation in acute lung injury.