Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan, China.
Biomed Pharmacother. 2020 May;125:109946. doi: 10.1016/j.biopha.2020.109946. Epub 2020 Jan 28.
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS.
A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested.
Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10.
Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.
急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）是一种以肺部迅速广泛炎症为特征的呼吸衰竭。姜黄素已被报道通过增强调节性 T 细胞（Tregs）的功能成为一种抗炎因子。本研究旨在探讨姜黄素对 Tregs 分化的影响，以及姜黄素在 ALI/ARDS 中的作用。
使用盲肠结扎穿孔（CLP）诱导的急性肺损伤小鼠模型来探讨姜黄素在 ALI/ARDS 中的作用。评估肺损伤的严重程度。检测肺组织中 IL-17A 和髓过氧化物酶（MPO）的免疫组化。检测血清和支气管肺泡灌洗液（BALF）中 Treg 相关细胞因子水平。检测肺组织中核因子-κB（NF-κB）的表达。通过免疫荧光检测肺组织中的巨噬细胞。定量脾 CD4+CD25+FOXP3+Tregs，评估 Tregs 从幼稚 CD4+T 细胞和 STAT5 的分化。检测体外幼稚 CD4+T 细胞分化过程中 IL-10 的表达。
姜黄素减轻了诱导的 CLP 小鼠模型中的肺损伤并抑制了炎症。姜黄素预处理后，CLP 小鼠肺部的 IL-17A、产生 MPO 的中性粒细胞和 NF-κB p65 的表达明显下降。我们发现姜黄素可以调节 CLP 小鼠肺部的 M1/M2 巨噬细胞水平。这可能是通过调节 Tregs 的分化和 Treg 衍生的 IL-10 的产生。Treg 衍生的 IL-10 是影响巨噬细胞极化的主要因素。我们发现姜黄素可以增加体内 Treg 比例，并上调 CLP 小鼠血清和 BALF 中的 IL-10 表达。在我们的体外实验中，我们发现姜黄素可以促进 Treg 分化并增加 IL-10 的产生。
姜黄素可以通过促进幼稚 CD4+T 细胞向 CD4+CD25+FOXP3+Tregs 的分化，减轻 ALI 和失控性炎症的严重程度。姜黄素促进巨噬细胞从 M1 向 M2 的转化。姜黄素诱导的 Tregs 分化可能是 IL-10 免疫调节的一个来源。
