Curcumin Promotes the Expression of IL-35 by Regulating Regulatory T Cell Differentiation and Restrains Uncontrolled Inf
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ORIGINAL ARTICLE
Curcumin Promotes the Expression of IL-35 by Regulating Regulatory T Cell Differentiation and Restrains Uncontrolled Inflammation and Lung Injury in Mice Yan-qing Chen,1 Yu-sen Chai,1 Ke Xie,1 Feng Yu,1,2 Chuan-jiang Wang,1 Shi-hui Lin,1 Yuan-zheng Yang,3,4 and Fang Xu 1,4
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. KEY WORDS: curcumin; interleukin-35; regulatory T cell; uncontrolled inflammation; acute lung injury.
1
Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 2 Department of Critical Care Medicine, Changshou People’s Hospital, Chongqing, China 3 Department of Critical Care Medicine, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China 4 To whom correspondence should be addressed to Yuan-zheng Yang at Department of Critical Care Medicine, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China. E-mail: [email protected]; and ; [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Chen, Chai, Xie, Yu, Wang, Lin, Yang, and Xu INTRODUCTION
MATERIALS AND METHODS
Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with high incidence and mortality. A global study conducted over fifty countries showed that 10.4% (95% confidence interval [CI], 10.0–10.7%) of the intensive care unit patients developed AR
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