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

Autophagy is a fundamental cellular process involved in defense against infection by intracellular pathogens (Casanova, 2017) . Although contradictory findings have been reported (Ho et al., 2016) , accumulating evidence suggest that autophagy plays a key role in sepsis, and has been considered a potential target for sepsis-induced immunosuppression (Ren, Zhang, Wu & Yao, 2017) . It is promising to focus on autophagy axis to unveil the mechanism of sepsis-induced immunosuppression and discover the novel immunoregulating therapies for sepsis. Artesunate (AS) is an effective and reliable anti-malarial drug with low toxicity (Burrows, Chibale & Wells, 2011; Clark, White, S, Gaunt, Winstanley & Ward, 2004) , which possesses several interesting effects such as anti-inflammation and other effects (Efferth, Dunstan, Sauerbrey, Miyachi & Chitambar, 2001; Li et al., 2008; Miranda et al., 2013; Wang et al., 2017) . Previously, we showed that AS protects septic animals by inhibiting pro-inflammatory cytokine release in cytokine storm stage (Li et al., 2008) , suggesting that AS could exhibit anti-inflammatory activity during the cytokine storm phase of sepsis. Herein, cecal ligation and puncture (CLP)-induced sepsis immunosuppression mice model was employed to . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi. org/10.1101 org/10. /2020 11 investigate the effect of AS on sepsis-induced immunosuppression and the lipopolysaccharide/endotoxin (LPS) tolerance cell model was established to unveil the underlying mechanism.