Curcumin Promotes the Expression of IL-35 by Regulating Regulatory T Cell Differentiation and Restrains Uncontrolled Inflammation and Lung Injury in Mice

• Published in: Inflammation 2020-10, Vol.43 (5), p.1913-1924
• Main Authors: Chen, Yan-qing, Chai, Yu-sen, Xie, Ke, Yu, Feng, Wang, Chuan-jiang, Lin, Shi-hui, Yang, Yuan-zheng, Xu, Fang
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; CD25 antigen; CD4 antigen; Cecum; Cell differentiation; Curcumin; Cytokines; Foxp3 protein; Immunology; Immunoregulation; Inflammation; Internal Medicine; Lungs; Lymphocytes T; NF-κB protein; Nuclear transport; Original Article; Pathology; Pharmacology/Toxicology; Respiratory distress syndrome; Rheumatology; Spleen; Stat5 protein; Therapeutic targets
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-020-01265-2

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.