Evidence map›Paper›PMID 29520027›Full record

ArticleNature communications2018

The oxidized phospholipid oxPAPC protects from septic shock by targeting the non-canonical inflammasome in macrophages.

Lan H Chu, Mohanalaxmi Indramohan, Rojo A Ratsimandresy, Anu Gangopadhyay, Emily P Morris, Denise M Monack, Andrea Dorfleutner, Christian Stehlik

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 1 pooled it
7.5field-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

124 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.

  1. Pooled it
  2. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
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  18. Advances inMicroorganisms · 2025
    Review
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  20. Article

64 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

8 authors at 3 institutions in 1 country.

Lan H ChuDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.
Mohanalaxmi IndramohanDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.
Rojo A RatsimandresyDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.
Anu GangopadhyayDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.
Emily P MorrisDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.
Denise M MonackDepartment of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, Stanford, California, 94305, USA.
Andrea DorfleutnerDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA. a-dorfleutner@northwestern.edu.
Christian StehlikDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA. c-stehlik@northwestern.edu.
Northwestern University · USRobert H. Lurie Comprehensive Cancer Center of Northwestern UniversityStanford University · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9M
The Role of Keratinocytes as Independent ThermosensorsP30AR057216 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PALLER, AMY S · 2009 to 2018
$6.0M
Regulation of cytosolic pattern recognition receptor signaling in macrophagesR01AI099009 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI STEHLIK, CHRISTIAN · 2013 to 2022
$4.7M
Molecular Regulation of Systemic InflammationR01AI120625 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DORFLEUTNER, ANDREA, STEHLIK, CHRISTIAN · 2016 to 2020
$2.0M
A Regulatory Checkpoint in the Pathogenesis of Inflammatory ArthritisR01AR064349 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI STEHLIK, CHRISTIAN · 2013 to 2017
$1.9M
Inflammasome Adaptor and Effectors in Cryopyrinopathies and Crystal ArthropathiesK01AR066739 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DORFLEUTNER, ANDREA · 2015 to 2019
$471k
A novel mouse model to monitor inflammasome activation in vivoR21AI120618 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DORFLEUTNER, ANDREA, STEHLIK, CHRISTIAN · 2015 to 2016
$425k
NCI NIH HHS P30 CA060553NIAID NIH HHS R01 AI099009NIAID NIH HHS R01 AI120625NIAID NIH HHS R21 AI120618NIAMS NIH HHS K01 AR066739NIAMS NIH HHS P30 AR057216NIAMS NIH HHS R01 AR064349
6 · The paper itself

Abstract

Lipopolysaccharide (LPS) of Gram-negative bacteria can elicit a strong immune response. Although extracellular LPS is sensed by TLR4 at the cell surface and triggers a transcriptional response, cytosolic LPS binds and activates non-canonical inflammasome caspases, resulting in pyroptotic cell death, as well as canonical NLRP3 inflammasome-dependent cytokine release. Contrary to the highly regulated multiprotein platform required for caspase-1 activation in the canonical inflammasomes, the non-canonical mouse caspase-11 and the orthologous human caspase-4 function simultaneously as innate sensors and effectors, and their regulation is unclear. Here we show that the oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) inhibits the non-canonical inflammasome in macrophages, but not in dendritic cells. Aside from a TLR4 antagonistic role, oxPAPC binds directly to caspase-4 and caspase-11, competes with LPS binding, and consequently inhibits LPS-induced pyroptosis, IL-1β release and septic shock. Therefore, oxPAPC and its derivatives might provide a basis for therapies that target non-canonical inflammasomes during Gram-negative bacterial sepsis.

Indexed as

AnimalsAnti-Inflammatory AgentsCaspasesCaspases, InitiatorCells, CulturedFemaleHumansInflammasomesInterleukin-1betaLipopolysaccharidesMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinAnti-Inflammatory AgentsCasp4 protein, mouseCaspasesCaspases, InitiatorInflammasomesInterleukin-1betaLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseoxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholinePhosphatidylcholines

Identifiers

PMID29520027
PMCPMC5843631
OpenAlexW2794112735

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.