Evidence map›Paper›PMID 40817837›Full record

ArticleJournal of leukocyte biology2025

Caspase-11 regulates systemic inflammation and cell death in a cell-specific manner after trauma with shock.

Joud Mulla, Alyssa Gregory, Hong Liao, Bashar Al Matour, Yuzhen Li, Abiha Abdullah, Timothy R Billiar, Melanie J Scott

Abstract read
In one paragraph

Article in Journal of leukocyte biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

8 authors.

Joud MullaDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.ORCID 0000-0002-3872-0404
Alyssa GregoryDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.ORCID 0000-0002-0392-7202
Hong LiaoDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.
Bashar Al MatourDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.ORCID 0009-0006-8847-0294
Yuzhen LiDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.ORCID 0009-0001-8154-9008
Abiha AbdullahDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.
Timothy R BilliarDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.ORCID 0000-0002-2949-0811
Melanie J ScottDepartment of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, United States.ORCID 0000-0001-6864-5970

Funding

Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Satdarshan Singh Monga · 2019 to 2026
$10.9M
Inflammasome activation in trauma-hemorrhagic shockR01GM102146 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCOTT, MELANIE J. · 2013 to 2025
$4.3M
NIDDK NIH HHS P30 DK120531NIGMS NIH HHS R01 GM102146NIH HHS NIH NIGMS R01GM102146
6 · The paper itself

Abstract

Severe trauma releases damage-associated molecular patterns (DAMPs), which activate the immune system via pattern recognition receptors. This triggers inflammatory cascades that can lead to systemic inflammatory response syndrome, immunosuppression, and multiple organ dysfunction syndrome. Pyroptosis is an inflammatory form of cell death mediated by caspase-11 and gasdermin D (GsdmD). In this study, we examined caspase-11's effects on inflammation, tissue damage, and neutrophil infiltration in a model of severe tissue injury. Male C57BL/6J (WT), caspase-11-/-, cell-specific caspase-11-/- mice (endothelial-specific caspase-11-/- [casp11EC-/-]), platelet-specific caspase-11-/- (casp11plt-/-), and hepatocyte-specific caspase-11-/- (casp11HC-/-) mice were subjected to polytrauma, consisting of hemorrhagic shock (25% total blood volume removed), liver crush, and bilateral lower extremity injury. At 6 h post-polytrauma, blood, plasma, and tissues were collected for analysis. Western blot analysis showed caspase-11 and GsdmD cleavage in the lungs and liver in WT mice at 6 h after polytrauma. GsdmD cleavage was found to be caspase-11 dependent. Inflammatory mediators, plasma IL-6 and CXCL-1/KC, were significantly increased in caspase-11-/-, casp11HC-/- and casp11EC-/- mice compared to WT controls or casp11plt-/-. Liver damage (ALT/AST) was similar between groups. Circulating neutrophil counts were decreased in caspase-11-/-, but neutrophils and neutrophil myeloperoxidase levels were increased in caspase-11-/- liver compared with WT after polytrauma. Our study identifies an unexpected and novel anti-inflammatory function for caspase-11 in trauma, through the regulation of neutrophil influx into tissues. Our findings underscore the significance of caspase-11 activation early after polytrauma to moderate trauma-induced inflammation.

Indexed as

CaspasesCaspases, InitiatorInflammationMultiple TraumaShock, HemorrhagicAnimalsCell DeathGasderminsMaleMiceMice, Inbred C57BLMice, KnockoutNeutrophil InfiltrationNeutrophilsPhosphate-Binding ProteinsPyroptosisCasp4 protein, mouseCaspasesCaspases, InitiatorGasderminsGsdmd protein, mousePhosphate-Binding Proteinscaspase-11inflammationprogrammed cell deathtissue injury

Identifiers

PMID40817837
PMCPMC12394988

What Socratic 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 Socratic graph.