2. Academic Validation
  3. Tabersonine attenuates lipopolysaccharide-induced acute lung injury via suppressing TRAF6 ubiquitination

Tabersonine attenuates lipopolysaccharide-induced acute lung injury via suppressing TRAF6 ubiquitination

  • Biochem Pharmacol. 2018 Aug;154:183-192. doi: 10.1016/j.bcp.2018.05.004.
Depeng Zhang 1,  Xiaozong Li 2,  Yudong Hu 3,  Hongchao Jiang 4,  Yaxian Wu 5,  Yunhe Ding 6,  Kaikai Yu 7,  Huiqiong He 8,  Jingsong Xu 9,  Lei Sun 10,  Feng Qian 11
Affiliations

Affiliations

  • 1 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: zdpkaka@sjtu.edu.cn.
  • 2 Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, PR China.
  • 3 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: ydhfighting@sjtu.edu.cn.
  • 4 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: jhc111vs@sjtu.edu.cn.
  • 5 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: yaxianwu@sjtu.edu.cn.
  • 6 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: yhding1993@sjtu.edu.cn.
  • 7 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: mr.right@sjtu.edu.cn.
  • 8 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: hhq@sjtu.edu.cn.
  • 9 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: jingsong.xu@scu.edu.cn.
  • 10 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: sunlei_vicky@sjtu.edu.cn.
  • 11 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221004, PR China; Research Center for Cancer Precision Medicine, Department of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, PR China. Electronic address: fengqian@sjtu.edu.cn.
PMID: 29746822 DOI: 10.1016/j.bcp.2018.05.004
Abstract

Sepsis caused by Gram-negative bacteria is one of major causes for the progression of acute lung injury (ALI) with limited treatment and effective medicines. Tabersonine is an indole alkaloid mainly isolated from Catharanthus roseus, and a potential drug candidate for treatment of Cancer and Alzheimer's disease (AD), however, its anti-inflammatory effect has not been revealed. In this study, we reported that tabersonine ameliorated lipopolysaccharides (LPS)-induced ALI in vivo and inhibited LPS-mediated macrophage activation in vitro. By using murine ALI model, we found that tabersonine significantly attenuated LPS-induced pathological injury in the lung. Tabersonine also inhibited LPS-mediated neutrophil infiltration, elevation of MPO activity and the production of TNF-α, IL-6 and IL-1β. Furthermore, tabersonine inhibited LPS-induced the production of pro-inflammatory mediators such as iNOS, NO and cytokines by suppressing NF-κB and p38 MAPK/MK2 signaling cascades. Tabersonine reduced the K63-linked polyubiquitination of TRAF6. Taken together, these results suggested that tabersonine has anti-inflammatory activities in vitro and in vivo, and is a potential therapeutic candidate for the treatment of ALI/ARDS.

Keywords

Acute lung injury; Inflammation; NF-κB; TRAF6; Tabersonine; p38.

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