The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death
Open accessAbstract
Gasdermin D (GSDMD) is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT) to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent. It was mediated by a neutrophil-specific serine protease, neutrophil elastase (ELANE), released from cytoplasmic granules into the cytosol in aging neutrophils. ELANE-mediated GSDMD cleavage was upstream of the caspase cleavage site and produced a fully active ELANE-derived NT fragment (GSDMD-eNT) that induced lytic cell death as efficiently as GSDMD-cNT. Thus, GSDMD is pleiotropic, exerting both pro- and anti-inflammatory effects that make it a potential target for antibacterial and anti-inflammatory therapies.
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Cites
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Kayagaki, N., Stowe, I. B., Lee, B. L., O’Rourke, K., Anderson, K., Warming, S., Cuellar, T., Haley, B., Roose-Girma, M., Phung, Q. T., et al. (2015) · Nature · doi:10.1038/nature15541 · Cited by 3,686
Self-citationInflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Pore-forming activity and structural autoinhibition of the gasdermin family
Ding, J., Wang, K., Liu, W., She, Y., Sun, Q., Shi, J., Sun, H., Wang, D.-C., & Shao, F. (2016) · Nature · doi:10.1038/nature18590 · Cited by 2,771
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Apoptotic cell clearance: basic biology and therapeutic potential
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Metzler, K. D., Goosmann, C., Lubojemska, A., Zychlinsky, A., & Papayannopoulos, V. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.044 · Cited by 741 · cited 5×
“A recent study showed that ELANE release during NETosis also is triggered by ROS (Metzler et al., 2014).”
BackgroundInfluentialNeutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP
Karmakar, M., Katsnelson, M. A., Dubyak, G. R., & Pearlman, E. (2016) · Nature Communications · doi:10.1038/ncomms10555 · Cited by 450
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Degradation of Outer Membrane Protein A in Escherichia coli Killing by Neutrophil Elastase
Belaaouaj, A. A., Kim, K. S., & Shapiro, S. D. (2000) · Science · doi:10.1126/science.289.5482.1185 · Cited by 363
Proteinase 3–dependent caspase-3 cleavage modulates neutrophil death and inflammation
Loison, F., Zhu, H., Karatepe, K., Kasorn, A., Liu, P., Ye, K., Zhou, J., Cao, S., Gong, H., Jenne, D. E., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci76246 · Cited by 145
Self-citation
Cited by
Pyroptosis: Mechanisms and Diseases
Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C., & Chen, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00507-5 · Cited by 2,353
Self-citationThe gasdermins, a protein family executing cell death and inflammation
Broz, P., Pelegrín, P., & Shao, F. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0228-2 · Cited by 1,641
Pyroptosis versus necroptosis: similarities, differences, and crosstalk
Frank, D., & Vince, J. E. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0212-6 · Cited by 1,062
Neutrophils and NETS in modulating acute and chronic inflammation
Castanheira, F. V. S., & Kubes, P. (2019) · Blood · doi:10.1182/blood-2018-11-844530 · Cited by 792
NETosis: Molecular Mechanisms, Role in Physiology and Pathology
Vorobjeva, N. V., & Chernyak, B. V. (2020) · Biochemistry (Moscow) · doi:10.1134/s0006297920100065 · Cited by 559
Metadata
- Authors
- Kambara, H., Liu, F., Zhang, X., Liu, P., Bajrami, B., Teng, Y., Zhao, L., Zhou, S., Yu, H., Zhou, W., Silberstein, L. E., Cheng, T., Han, M., Xu, Y., & Luo, H. R.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 22
- Issue
- 11
- Pages
- 2924-2936
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2792307022
- Cited by
- 419
- References
- 10
- FWCI
- 10.59
- Type
- journal article
- Language
- en
- Open access
- gold
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- Kambara, H., Liu, F., Zhang, X., Liu, P., Bajrami, B., Teng, Y., Zhao, L., Zhou, S., Yu, H., Zhou, W., Silberstein, L. E., Cheng, T., Han, M., Xu, Y., & Luo, H. R. (2018). Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death. Cell Reports. https://doi.org/10.1016/j.celrep.2018.02.067
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