As a Chinese traditional patent medicine, Tripterygium wilfordii glycosides (TWG) have been approved by the China State Food and Drug Administration (Z32021007) for autoimmune and inflammatory diseases. Application of TWG leads to significant decrease of the inflammatory cytokines, such as IL-6, IL-1β, and TNF-α. However, little is known whether TWG could regulate the anti-inflammatory cytokines and what the mechanism is. Here, we found that TWG could induce the upregulation of IL-37 which is a new anti-inflammatory cytokine. Furthermore, the inhibitors of ERK1/2 and/or p38 MAPK pathways suppressed IL-37 expression induced by TWG, indicating that the two pathways took part in this process. In conclusion, TWG could upregulate the anti-inflammatory cytokine IL-37 and ERK1/2 and p38 MAPK signal pathways were involved in the upregulation of IL-37 induced by TWG. The results showed that TWG had a potent activity on promoting the expression of IL-37, a new anti-inflammatory cytokine, which help further understanding the anti-inflammatory mechanism for the clinical application of TWG in therapy of diseases.

as a novel anti-inflammatory cytokine of the interleukin (il)-1 family, il-37 protects the human body from diseases characterized by excessive inflammation. The pathologic process of hyperhomocysteinemia (hHcy) is accompanied by persistent inflammation. However, little is known regarding the role of IL-37 in hHcy. In the present study, the levels of cytokines including il-37, il-1β, il-6 and tumor necrosis factor-α in the supernatant were detected by ELISA. mRNA and protein expression were detected by Reverse transcription-quantitative PCR and western blotting, respectively. LDH level was determined by ELISA and the cell viability was detected through CCK-8 kit. In the present study, mean serum IL-37 levels of patients with hHcy were 32.3% lower than those of controls (P<0.01). In peripheral blood mononuclear cells (PBMCs) from patients with hHcy, mean IL-37 mRNA expression was 73.5% lower (P<0.01) and IL-37 protein expression was 77.7% lower compared with that of healthy controls (P<0.01). Furthermore, the results demonstrated that exogenous homocysteine (Hcy) stimulation markedly downregulated the mRNA and protein expression levels of il-37 in PBMcs in vitro. in 293T cells, overexpression of il-37 restored the cell viability impaired by Hcy, and reduced the release of lactate dehydrogenase and the proinflammatory cytokines IL-1β, il-6 and tumor necrosis factor-α. In conclusion, IL-37 was downregulated by Hcy in vivo and in vitro, and il-37 exhibited a protective role against cell injury induced by Hcy.