Inhibition of Dpp8/9 activates the Nlrp1b inflammasome Journal Article

   


Authors: Okondo, M. C.; Rao, S. D.; Taabazuing, C. Y.; Chui, A. J.; Poplawski, S. E.; Johnson, D. C.; Bachovchin, D. A.
Article Title: Inhibition of Dpp8/9 activates the Nlrp1b inflammasome
Abstract: Val-boroPro (PT-100, Talabostat) induces powerful anti-tumor immune responses in syngeneic cancer models, but its mechanism of action has not yet been established. Val-boroPro is a non-selective inhibitor of post-proline-cleaving serine proteases, and the inhibition of the highly related cytosolic serine proteases Dpp8 and Dpp9 (Dpp8/9) by Val-boroPro was recently demonstrated to trigger an immunostimulatory form of programmed cell death known as pyroptosis selectively in monocytes and macrophages. Here we show that Dpp8/9 inhibition activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis. This work reveals a previously unrecognized mechanism for activating an innate immune pattern recognition receptor and suggests that Dpp8/9 serve as an intracellular checkpoint to restrain Nlrp1b and the innate immune system. Dpp8/9 inhibitors induce an inflammatory form of cell death called pyroptosis in monocytes and macrophages. Here, Okondo et al. show that Dpp8/9 inhibition activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis. This work reveals a previously unrecognized mechanism for stimulating the innate immune system. © 2017 Elsevier Ltd
Keywords: pyroptosis; caspase-1; dpp8/9; nlrp1b inflammasome; val-boropro
Journal Title: Cell Chemical Biology
Volume: 25
Issue: 3
ISSN: 2451-9456
Publisher: Cell Press  
Date Published: 2018-03-15
Start Page: 262
End Page: 267.e5
Language: English
DOI: 10.1016/j.chembiol.2017.12.013
PROVIDER: scopus
PMCID: PMC5856610
PUBMED: 29396289
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041014720&doi=10.1016%2fj.chembiol.2017.12.013&partnerID=40&md5=4062ea258acd5ce88fcf9d47efd31481
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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MSK Authors
  1. Marian Okondo
    8 Okondo
  2. Daniel Bachovchin
    35 Bachovchin
  3. Cornelius Y Taabazuing
    9 Taabazuing
  4. Darren Christopher Johnson
    14 Johnson
  5. Sahana Dinesh Rao
    13 Rao
  6. Ashley Jeng-yun Chui
    11 Chui
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