BPTES inhibits anthrax lethal toxin-induced inflammatory response
Copyright © 2020 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:85 |
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| Enthalten in: |
International immunopharmacology - 85(2020) vom: 16. Aug., Seite 106664 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jinling [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.04.2021 Date Revised 21.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2020.106664 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM311007732 |
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| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anthrax lethal toxin | |
| 650 | 4 | |a BPTES | |
| 650 | 4 | |a Inflammatory response | |
| 650 | 4 | |a NLRP1b | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Antigens, Bacterial |2 NLM | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 650 | 7 | |a Bacterial Toxins |2 NLM | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a NALP1 protein, mouse |2 NLM | |
| 650 | 7 | |a Sulfides |2 NLM | |
| 650 | 7 | |a Thiadiazoles |2 NLM | |
| 650 | 7 | |a anthrax toxin |2 NLM | |
| 650 | 7 | |a bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide |2 NLM | |
| 700 | 1 | |a Yang, Daowei |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Xizi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junsheng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaomei |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Jinzhou |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Jiaying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yilin |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Zhongquan |e verfasserin |4 aut | |
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