Evidence map›Paper›PMID 29539421›Full record

ArticleCell reports2018

Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death.

Hiroto Kambara, Fei Liu, Xiaoyu Zhang, Peng Liu, Besnik Bajrami, Yan Teng, Li Zhao, Shiyi Zhou, Hongbo Yu, Weidong Zhou and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
259citing papers in PubMed, 1 pooled it
12.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

259 citing papers in PubMed, 1 synthesis or guideline pooled it, 410 citations in OpenAlex.

  1. Review: the role of GSDMD in sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Pooled it
  2. Prognostic model construction and drug prediction in colorectal cancer using mitochondrial programmed cell death-related genes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  3. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. How to recognize if a cell dies from pyroptosis?Molecular biology reports · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Pyroptosis: Turning Up the Heat on Cancer.Annual review of immunology · 2026
    Review
  14. Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026
    Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

199 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 8 institutions in 2 countries.

Hiroto KambaraDepartment of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Department of Laboratory Medicine, Children's Hospital Boston, Enders Research Building, Room 814, Boston, MA 02115, USA.
Fei LiuThe State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Xiaoyu ZhangDepartment of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Department of Laboratory Medicine, Children's Hospital Boston, Enders Research Building, Room 814, Boston, MA 02115, USA; The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Peng LiuThe State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Besnik BajramiCenter for Development of Therapeutics, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Yan TengDepartment of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Department of Laboratory Medicine, Children's Hospital Boston, Enders Research Building, Room 814, Boston, MA 02115, USA.
Li ZhaoDepartment of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Department of Laboratory Medicine, Children's Hospital Boston, Enders Research Building, Room 814, Boston, MA 02115, USA.
Shiyi ZhouDepartment of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Department of Laboratory Medicine, Children's Hospital Boston, Enders Research Building, Room 814, Boston, MA 02115, USA.
Hongbo YuVA Boston Healthcare System, Department of Pathology and Laboratory Medicine, Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
Weidong ZhouCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
Leslie E SilbersteinDepartment of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Department of Laboratory Medicine, Children's Hospital Boston, Enders Research Building, Room 814, Boston, MA 02115, USA.
Tao ChengThe State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Mingzhe HanThe State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Yuanfu XuThe State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Hongbo R LuoDepartment of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA; Department of Laboratory Medicine, Children's Hospital Boston, Enders Research Building, Room 814, Boston, MA 02115, USA. Electronic address: hongbo.luo@childrens.harvard.edu.
Boston Children's Hospital · USChinese Academy of Medical Sciences & Peking Union Medical College · CNDana-Farber/Harvard Cancer Center · USInstitute of Hematology & Blood Diseases Hospital · CNBroad Institute · USGeorge Mason University · USHarvard University · USVA Boston Healthcare System · US

Funding

Transcription regulation in hematopoiesisP01HL095489 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI PARK, SHINYOUNG · 2010 to 2020
$20.1M
Enhancing neutrophil function in neutropenia-related pneumoniaR01HL092020 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI LUO, HONGBO R · 2009 to 2022
$5.2M
Regulation of neutrophil function by ROS-induced actin glutathionylationR01AI103142 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LUO, HONGBO R · 2014 to 2018
$2.2M
HTS for enhancers of neutrophil function that specifically augment PIP3 signalR01AI076471 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LUO, HONGBO R · 2009 to 2012
$1.5M
Signal transduction in neutrophil chemotaxisR01GM076084 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI LUO, HONGBO R · 2006 to 2010
$1.5M
NHLBI NIH HHS P01 HL095489NHLBI NIH HHS R01 HL092020NIAID NIH HHS R01 AI076471NIAID NIH HHS R01 AI103142NIGMS NIH HHS R01 GM076084
6 · The paper itself

Abstract

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.

Indexed as

AnimalsAnti-Inflammatory AgentsApoptosis Regulatory ProteinsCell DeathGasderminsHumansIntracellular Signaling Peptides and ProteinsMiceNeutrophilsPhosphate-Binding ProteinsAnti-Inflammatory AgentsApoptosis Regulatory ProteinsGasderminsGsdmd protein, mouseIntracellular Signaling Peptides and ProteinsPhosphate-Binding ProteinsGSDMDhost defenseinnate immunityneutrophil deathneutrophil elastase

Identifiers

PMID29539421
PMCPMC5878047
OpenAlexW2792307022

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.