1. Academic Validation
  2. BPTES inhibits anthrax lethal toxin-induced inflammatory response

BPTES inhibits anthrax lethal toxin-induced inflammatory response

  • Int Immunopharmacol. 2020 Aug;85:106664. doi: 10.1016/j.intimp.2020.106664.
Jinling Wang 1 Daowei Yang 2 Xizi Shen 3 Junsheng Wang 1 Xiaomei Liu 1 Jinzhou Lin 1 Jiaying Zhong 4 Yilin Zhao 5 Zhongquan Qi 6
Affiliations

Affiliations

  • 1 Department of Emergency, Zhongshan Hospital of Xiamen University, Xiamen 361005, China.
  • 2 Department of Emergency, Zhongshan Hospital of Xiamen University, Xiamen 361005, China. Electronic address: [email protected].
  • 3 Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • 4 Faculty of Medicine, Xiamen University, Xiamen, China.
  • 5 Department of Oncology and Vascular Interventional Radiology, Zhongshan Hospital of Xiamen University, Xiamen, China.
  • 6 School of Medicine, Guangxi University, Nanning 530004, China. Electronic address: [email protected].
Abstract

Bacillus anthracis is a lethal agent of anthrax disease and the toxins are required in anthrax pathogenesis. The anthrax lethal toxin can trigger NLRP1b inflammasome activation and Pyroptosis. Although the underlying mechanism is well understood, the medications targeting the NLRP1b inflammasome are not available in the clinic. Herein, we describe that BPTES, a known Glutaminase (GLS) inhibitor, is an effective NLRP1b inflammasome inhibitor. BPTES could effectively and specifically suppress NLRP1b inflammasome activation in macrophages but have no effects on NLRP3, NLRC4 and AIM2 inflammasome activation. Mechanistically, BPTES alleviated the UBR2 mediated proteasomal degradation pathway of the NLRP1b N terminus, thus blocking the release of the CARD domain for subsequent Caspase-1 processing. Furthermore, BPTES could prevent disease progression in mice challenged with the anthrax lethal toxin. Taken together, our studies indicate that BPTES can be a promising pharmacological inhibitor to treat anthrax lethal toxin-related inflammatory diseases.

Keywords

Anthrax lethal toxin; BPTES; Inflammatory response; NLRP1b.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12683
    98.75%, Glutaminase Inhibitor