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Cited by 608

The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.

Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis

Open access
Kang, Rui, Zeng, Ling, Zhu, Shan, Xie, Yangchun, Liu, Jiao, Wen, Qirong, Cao, Lizhi, Xie, Min, Ran, Qitao, Kroemer, Guido, Wang, Haichao, Billiar, Timothy R., Jiang, Jianxin, Tang, Daolin·2018·Cell Host & Microbe

Abstract

Summary Sepsis is a life-threatening condition caused by pathogen infection and associated with pyroptosis. Pyroptosis occurs upon activation of proinflammatory caspases and their subsequent cleavage of gasdermin D (GSDMD), resulting in GSDMD N-terminal fragments that form membrane pores to induce cell lysis. Here, we show that antioxidant defense enzyme glutathione peroxidase 4 (GPX4) and its ability to decrease lipid peroxidation, negatively regulate macrophage pyroptosis, and septic lethality in mice. Conditional Gpx4 knockout in myeloid lineage cells increases lipid peroxidation-dependent caspase-11 activation and GSDMD cleavage. The resultant N-terminal GSDMD fragments then trigger macrophage pyroptotic cell death in a phospholipase C gamma 1 (PLCG1)-dependent fashion. Administration of the antioxidant vitamin E that reduces lipid peroxidation, chemical inhibition of PLCG1, or genetic Caspase-11 or Gsdmd inactivation prevents polymicrobial sepsis in Gpx4−/− mice. Collectively, this study suggests that lipid peroxidation drives GSDMD-mediated pyroptosis and hence constitutes a potential therapeutic target for lethal infection.

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Crossref · 10.1016/j.chom.2018.05.009

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Metadata

Authors
Kang, R., Zeng, L., Zhu, S., Xie, Y., Liu, J., Wen, Q., Cao, L., Xie, M., Ran, Q., Kroemer, G., Wang, H., Billiar, T. R., Jiang, J., & Tang, D.
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2018-07
Volume
24
Issue
1
Pages
97-108.e4
ISSN
1931-3128 (ISSN-L)
OpenAlex
W2808965517
Cited by
608
References
18
FWCI
12.48
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis. https://app.cochat.ai/papers/10.1016/j.chom.2018.05.009
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Kang, R., Zeng, L., Zhu, S., Xie, Y., Liu, J., Wen, Q., Cao, L., Xie, M., Ran, Q., Kroemer, G., Wang, H., Billiar, T. R., Jiang, J., & Tang, D. (2018). Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2018.05.009

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.