Evidence map›Paper›PMID 23708522›Full record

ArticleCell cycle (Georgetown, Tex.)2013

Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death.

Heriberto Lima, Lee S Jacobson, Michael F Goldberg, Kartik Chandran, Felipe Diaz-Griffero, Michael P Lisanti, Jürgen Brojatsch

Open access · hybridAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Cardio-Rheumatic Diseases: Inflammasomes Behaving Badly.International journal of molecular sciences · 2025
    Review
  11. NLRP3 inflammasome in health and disease (Review).International journal of molecular medicine · 2025
    Review
  12. Article
  13. Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.Journal of biochemical and molecular toxicology · 2025
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Heriberto LimaAlbert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, NY, USA.
Lee S Jacobson
Michael F Goldberg
Kartik Chandran
Felipe Diaz-Griffero
Michael P Lisanti
Jürgen Brojatsch
Albert Einstein College of Medicine · USBipar · FRYeshiva University · US

Funding

Role of Cellular Factors in Retroviral Uncoating and Synthesis of Viral DNAR01AI087390 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI DIAZ-GRIFFERO, FELIPE · 2010 to 2024
$6.8M
Mechanisms of Ebolavirus and Marburgvirus Entry into CellsR01AI088027 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CHANDRAN, KARTIK · 2010 to 2014
$2.0M
The Role of Cathepsins in Cell Death Mediated by NLR InducersR56AI092497 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI BROJATSCH, JURGEN · 2011 to 2011
$249k
NIAID NIH HHS 1R56AI092497-01A1NIAID NIH HHS R01 AI087390NIAID NIH HHS R56 AI092497
6 · The paper itself

Abstract

The Nod-like receptor, Nlrp3, has been linked to inflammatory diseases and adjuvant-mediated immune responses. A wide array of structurally diverse agents does not interact directly with Nlrp3, but is thought to activate the Nlrp3 inflammasome by inducing a common upstream signal, such as lysosome rupture. To test the connection between lysosome integrity and Nlrp3 signaling, we analyzed inflammasome activation following stimulation of murine macrophages with lysosome-destabilizing agents and pyroptosis inducers. Here we provide evidence that lysosomal rupture and the corresponding release of lysosomal hydrolases is an early event in macrophages exposed to the lysosome-destabilizing adjuvants LLOMe and alum. Lysosome rupture preceded cell death induction mediated by these agents and was associated with the degradation of low-molecular weight proteins, including the inflammasome component caspase-1. Proteolysis of caspase-1 was controlled by specific cathepsins, but was independent of autocatalytic processes and Nlrp3 signaling. Consistent with these findings, lysosome-disrupting agents triggered only minimal caspase-1 activation and failed to cause caspase-1-dependent cell death (pyroptosis), generally associated with Nlrp3 signaling. In contrast, lysosome rupture was a late event in macrophages exposed to prototypical pyroptosis inducers. These agents triggered extensive Nlrp3 signaling prior to lysosome rupture with only minimal impact on the cellular proteome. Taken together, our findings suggest that lysosome impairment triggers a cascade of events culminating in cell death but is not crucial for Nlrp3 signaling. The significant differences observed between lysosome-disrupting agents and pyroptosis inducers might explain the distinct immunologic responses associated with these compounds.

Indexed as

Alum CompoundsAnimalsApoptosisBlotting, WesternCarrier ProteinsCaspase 1Cell LineDipeptidesEnzyme-Linked Immunosorbent AssayInflammasomesLysosomesMiceMice, Inbred BALB CMice, Inbred C57BLNecrosisNLR Family, Pyrin Domain-Containing 3 ProteinAlum Compoundsaluminum sulfateCarrier ProteinsCaspase 1DipeptidesInflammasomesleucyl-leucine-methyl esterNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousecaspase-1lysosome rupturenecrosisNlrp3 inflammasomepyroptosis

Identifiers

PMID23708522
PMCPMC3735701
OpenAlexW2130904379

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.