Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy

Shenglan Shang; Jiaqi Wu; Xiaoli Li; Xin Liu; Pan Li; Chunli Zheng; Yonghua Wang; Songqing Liu; Jiang Zheng; Hong Zhou

To correlate the aforementioned findings from in vitro experiments, the mRNA and protein levels of VDR were measured in CLP mice. The results showed that the levels of VDR mRNA and protein expression significantly increased in PMs of CLP mice, but were markedly inhibited by AS (Figure 7a) , which was consistent with in vitro results. In VDR-KD CLP mice which VDR expression was knocked down using a lentiviral vector harboring a VDR RNAi sequence (VDR-KD) ( Figure S5a, b) , the level of TNF-α in spleen and lungs was significantly increased compare with negative control, and AS administration made no difference (Figure 7b ). It suggested that VDR overexpression is involved in sepsis-induced immunosuppression formulation, and knocking down of VDR would lead to loss of immunosuppressing phenotype. Additionally, immunoblotting results showed that autophagy-associated proteins in the spleen of CLP mice were increased compare with negative control, and AS made no difference (Figure 7c ). Taken together, both the in vivo and in vitro results indicate that the VDR plays an important role in sepsis-induced immunosuppression and AS's effect.