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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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Abstract

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 differentiation in vitro was 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.

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Acknowledgments

We are very grateful to the laboratory of Lipid & Glucose Metabolism at the First Affiliated Hospital of Chongqing Medical University to provide laboratory facilities.

Funding

This study was supported by the National Natural Science Foundation of China (81873928 to FX, 81760341 to YZ-Y, 81801894 to SH-L), Basic Science and Cutting-Edge Technology Research Projects of Chongqing Science and Technology Commission (cstc2019jcyjA0502, to SH-L), and Chinese Medicine Science and Technology Project of Chongqing City Health and Family Planning Committee (ZY201702071 to FX, 2019ZY3434 to SH-L).

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Authors and Affiliations

  1. Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Yan-qing Chen, Yu-sen Chai, Ke Xie, Feng Yu, Chuan-jiang Wang, Shi-hui Lin & Fang Xu

  2. Department of Critical Care Medicine, Changshou People’s Hospital, Chongqing, China

    Feng Yu

  3. Department of Critical Care Medicine, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China

    Yuan-zheng Yang

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  1. Yan-qing Chen
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  2. Yu-sen Chai
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  4. Feng Yu
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  7. Yuan-zheng Yang
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  8. Fang Xu
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Contributions

Conception hypothesis and design: Fang Xu and Yuan-zheng Yang. Data acquisition and analysis: Yan-qing Chen, Yu-sen Chai, and Ke Xie. Manuscript preparation: Yan-qing Chen and Fang Xu. Searched and collected bibliography: Shi-hui Lin and Chuan-jiang Wang.

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Correspondence to Yuan-zheng Yang or Fang Xu.

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The authors declare that they have no conflict of interest.

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This study was approved by the Ethics Committees of the First Affiliated Hospital of Chongqing Medical University (2016–34).

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Chen, Yq., Chai, Ys., Xie, K. et al. Curcumin Promotes the Expression of IL-35 by Regulating Regulatory T Cell Differentiation and Restrains Uncontrolled Inflammation and Lung Injury in Mice. Inflammation 43, 1913–1924 (2020). https://doi.org/10.1007/s10753-020-01265-2

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