Nemonoxacin Has Immunoprotective Effects on Reducing Mortality in Lipopolysaccharide-Induced Mouse Sepsis Model
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ORIGINAL ARTICLE
Nemonoxacin Has Immunoprotective Effects on Reducing Mortality in Lipopolysaccharide-Induced Mouse Sepsis Model Nanye Chen,1,2 Xin Li,1,3 Beining Guo,1,3 Jun Zou,4 Dongfang Lin,1,3 Xiang Li,5 Jinwei Huang,6 Meiqing Feng,7,8 and Xu Zhao 1,3,8
Nemonoxacin is a novel non-fluorinated quinolone. The effect of nemonoxacin on modulation of host immune response is not known. We sought to determine whether nemonoxacin has immunoprotective effects on lipopolysaccharide (LPS)-induced mouse sepsis model. Therefore, mice were challenged with lethal dose LPS (12.5 mg/kg) only or LPS with multi-dose nemonoxacin (40 mg/kg q12h) by intraperitoneal injection, and the results showed nemonoxacin could significantly reduce mortality from 80 to 30% in this model. The effect of nemonoxacin on immune cells in vivo and in vitro was also investigated. Mice were treated with sublethal LPS (5 mg/kg) or LPS + nemonoxacin, the myeloid cell
Abstract—
Nanye Chen and Xin Li contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-020-01296-9) contains supplementary material, which is available to authorized users. 1
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China 2 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, China 3 Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China 4 Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA 5 Minhang Hospital, Fudan University, Shanghai, China 6 The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China 7 Minhang Hospital & School of Pharmacy, Department of Biological Medicines Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China 8 To whom correspondence should be addressed to Meiqing Feng at Minhang Hospital & School of Pharmacy, Department of Biological Medicines Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China. E-mail: [email protected]; and ; [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Chen, Li, Guo, Zou, Lin, Li, Huang, Feng, and Zhao subsets in mouse spleen were analyzed by flow cytometry, and cytokines in mouse serum were measured by ELISA. Additionally, mouse macrophage RAW264.7 cells were treated with LPS or LPS + nemonoxacin to investigate the immune modulatory effect of nemonoxacin in vitro, and the level of cytokines in cell culture supernatant was determined by ELISA. Analysis of myeloid cell subsets in the spleen showed nemonoxacin pretreatment could significantly inhibit LPS-induced proliferation of macrophages and dendritic cells but have no effect on neutrophils. Nemonoxacin could significantly reduce the expression of proinflammatory cytokines IL-6 and TNF-α while increase anti-inflammatory cytokine IL-10 expression, which wer
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