Evidence map›Paper›PMID 33535228›Full record

ArticleThe Journal of cell biology2021

Brd4 regulates NLRC4 inflammasome activation by facilitating IRF8-mediated transcription of Naips.

Xingchen Dong, Xiangming Hu, Yan Bao, Guo Li, Xiao-Dong Yang, James M Slauch, Lin-Feng Chen

Open access · greenAbstract read
In one paragraph

Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Journal of medical microbiology · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. TLR priming licenses NAIP inflammasome activation by immunoevasive ligands.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Review
  9. BRD4 Regulates Glycolysis-Dependent Nos2 Expression in Macrophages Upon H pylori Infection.Cellular and molecular gastroenterology and hepatology · 2024
    Article
  10. Salmonella spvC gene suppresses macrophage/neutrophil antibacterial defense mediated by gasdermin D.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Article
  11. Review
  12. Role of pyroptosis in inflammation and cancer.Cellular & molecular immunology · 2022
    Review
  13. Chromatin structure undergoes global and local reorganization during murine dendritic cell development and activation.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  14. A BRD4 PROTAC nanodrug for glioma therapyActa pharmaceutica Sinica. B · 2022
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

7 authors at 3 institutions in 2 countries.

Xingchen DongDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL.
Xiangming HuFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Yan BaoDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL.
Guo LiFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Xiao-Dong YangShanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
James M SlauchDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL.
Lin-Feng ChenDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL.
University of Illinois Urbana-Champaign · USFujian Medical University · CNShanghai Jiao Tong University · CN

Funding

Characterizing the targets of phagocytic superoxide in SalmonellaR01AI123381 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI SLAUCH, JAMES M. · 2016 to 2019
$1.5M
NIAID NIH HHS R01 AI123381
6 · The paper itself

Abstract

NLRC4 inflammasome activation and the subsequent maturation of IL-1β and IL-18 are critical for protection against infection by bacterial pathogens. The epigenetic regulator Brd4 has emerged as a key player in inflammation by regulating the expression of inflammatory cytokines. However, whether Brd4 has any role in inflammasome activation remains undetermined. Here, we demonstrated that Brd4 is an important regulator of NLRC4 inflammasome activation in response to Salmonella typhimurium infection. Brd4-deficient bone marrow-derived macrophages (BMDMs) displayed impaired caspase-1 activation, ASC oligomerization, IL-1β maturation, gasdermin-D cleavage, and pyroptosis in response to S.typhimurium infection. RNA sequencing and RT-PCR results revealed that the transcription of Naips was decreased in Brd4-deficient BMDMs. Brd4 formed a complex with IRF8/PU.1 and bound to the IRF8 and PU.1 binding motifs on the promoters of Naips to maintain the expression of Naips. Furthermore, myeloid lineage-specific Brd4 conditional knockout mice were more susceptible to S.typhimurium infection with increased mortality, bacterial loads, and tissue damage; impaired inflammasome-dependent cytokine production; and pyroptosis. Our studies identify a novel function of Brd4 in innate immunity by controlling inflammasome-mediated cytokine release and pyroptosis to effectively battle S.typhimurium infection.

Indexed as

Transcription, GeneticAnimalsApoptosis Regulatory ProteinsBase SequenceBromodomain Containing ProteinsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCpG IslandsGasderminsInflammasomesInterferon Regulatory Factor-8Interferon Regulatory FactorsIntracellular Signaling Peptides and ProteinsMacrophagesMiceMice, KnockoutApoptosis Regulatory ProteinsBrd4 protein, mouseBromodomain Containing ProteinsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsGasderminsGsdmd protein, mouseInflammasomesInterferon Regulatory Factor-8Interferon Regulatory FactorsIntracellular Signaling Peptides and ProteinsIpaf protein, mouseNeuronal Apoptosis-Inhibitory ProteinNuclear ProteinsPhosphate-Binding ProteinsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Pycard protein, mouseTrans-ActivatorsTranscription Factors

Identifiers

PMID33535228
PMCPMC7863722
OpenAlexW3127614035

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.