Evidence map›Paper›PMID 27385778›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2016

Active Caspase-1 Induces Plasma Membrane Pores That Precede Pyroptotic Lysis and Are Blocked by Lanthanides.

Hana M Russo, Joseph Rathkey, Andrea Boyd-Tressler, Michael A Katsnelson, Derek W Abbott, George R Dubyak

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed
9.4field-weighted citation impact, top 2% 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

127 citing papers in PubMed, 185 citations in OpenAlex.

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67 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

6 authors at 1 institution in 1 country.

Hana M RussoDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;
Joseph RathkeyDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;
Andrea Boyd-TresslerDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH 44106; and.ORCID 0000-0003-4209-2188
Michael A KatsnelsonDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;
Derek W AbbottDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;ORCID 0000-0003-4387-8094
George R DubyakDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106; and Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106 george.dubyak@case.edu.ORCID 0000-0001-9720-4226
Case Western Reserve University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Ubiquitination Pathways Mediating Chronic Intestinal InflammationP01DK091222 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI COMINELLI, FABIO · 2011 to 2020
$16.5M
The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Theresa Torres Pizarro · 2015 to 2026
$15.6M
Toll Like Receptors in Bacterial KeratitisR01EY014362 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI GEORGE R DUBYAK, Eric Pearlman · 2003 to 2026
$8.7M
TRANSMEMBRANE SIGNALLING IN SMOOTH MUSCLE CELL LINESR01GM036387 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI DUBYAK, GEORGE R · 1987 to 2014
$4.5M
Innate Immune Signal Transduction Specificity in Inflammatory DiseaseR01GM086550 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI ABBOTT, DEREK W · 2009 to 2020
$3.8M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
Cardiovascular Research Training Program (CRTP)T32HL105338 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI JAIN, MUKESH KUMAR · 2010 to 2014
$1.8M
NEI NIH HHS R01 EY014362NHLBI NIH HHS T32 HL105338NIAID NIH HHS T32 AI089474NIDDK NIH HHS P01 DK091222NIDDK NIH HHS P30 DK097948NIGMS NIH HHS R01 GM036387NIGMS NIH HHS R01 GM086550NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

Canonical inflammasome activation induces a caspase-1/gasdermin D (Gsdmd)-dependent lytic cell death called pyroptosis that promotes antimicrobial host defense but may contribute to sepsis. The nature of the caspase-1-dependent change in plasma membrane (PM) permeability during pyroptotic progression remains incompletely defined. We assayed propidium(2+) (Pro(2+)) influx kinetics during NLRP3 or Pyrin inflammasome activation in murine bone marrow-derived macrophages (BMDMs) as an indicator of this PM permeabilization. BMDMs were characterized by rapid Pro(2+) influx after initiation of NLRP3 or Pyrin inflammasomes by nigericin (NG) or Clostridium difficile toxin B (TcdB), respectively. No Pro(2+) uptake in response to NG or TcdB was observed in Casp1(-/-) or Asc(-/-) BMDMs. The cytoprotectant glycine profoundly suppressed NG and TcdB-induced lysis but not Pro(2+) influx. The absence of Gsdmd expression resulted in suppression of NG-stimulated Pro(2+) influx and pyroptotic lysis. Extracellular La(3+) and Gd(3+) rapidly and reversibly blocked the induced Pro(2+) influx and markedly delayed pyroptotic lysis without limiting upstream inflammasome assembly and caspase-1 activation. Thus, caspase-1-driven pyroptosis requires induction of initial prelytic pores in the PM that are dependent on Gsdmd expression. These PM pores also facilitated the efflux of cytosolic ATP and influx of extracellular Ca(2+) Although lanthanides and Gsdmd deletion both suppressed PM pore activity and pyroptotic lysis, robust IL-1β release was observed in lanthanide-treated BMDMs but not in Gsdmd-deficient cells. This suggests roles for Gsdmd in both passive IL-1β release secondary to pyroptotic lysis and in nonlytic/nonclassical IL-1β export.

Indexed as

AnimalsApoptosis Regulatory ProteinsCaspase 1Cell MembraneGasderminsInflammasomesInterleukin-1betaIntracellular Signaling Peptides and ProteinsLanthanoid Series ElementsMacrophagesMiceMice, Inbred C57BLMice, KnockoutPhosphate-Binding ProteinsPyroptosisApoptosis Regulatory ProteinsCaspase 1GasderminsGsdmd protein, mouseInflammasomesInterleukin-1betaIntracellular Signaling Peptides and ProteinsLanthanoid Series ElementsPhosphate-Binding Proteins

Identifiers

PMID27385778
PMCPMC4976007
OpenAlexW2469002912

What OpenQuestion holds

Textmetadata
LicenceTDM
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.