Indole derivative XCR-5a alleviates LPS-induced inflammation in vitro and in vivo

体内 脂多糖 炎症 肿瘤坏死因子α 药理学 一氧化氮合酶 化学 体外 一氧化氮 细胞因子 促炎细胞因子 免疫学 生物 生物化学 生物技术 有机化学
作者
Jiajing Zhao,Prasanta Roy,Haimei Tang,Xingyu Ma,Qianqian Di,Jiazheng Quan,Yonghong Guan,Xiao-Li Li,Wei-Lie Xiao,Weilin Chen
出处
期刊:Immunopharmacology and Immunotoxicology [Informa]
卷期号:: 1-11
标识
DOI:10.1080/08923973.2021.2020284
摘要

Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo.This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms.First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1β, IL-6, and TNF-α was determined and H&E staining was performed.Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1β, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway.XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases.
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