Evidence map›Paper›PMID 26269588›Full record

ArticleThe Journal of biological chemistry2015

Neutrophil elastase promotes interleukin-1β secretion from human coronary endothelium.

Mabruka Alfaidi, Heather Wilson, Marc Daigneault, Amanda Burnett, Victoria Ridger, Janet Chamberlain, Sheila Francis

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
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  12. Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
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  19. Extracellular Vesicles and Ischemic Cardiovascular Diseases.Advances in experimental medicine and biology · 2023
    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 1 institution in 1 country.

Mabruka AlfaidiFrom the Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom.
Heather WilsonFrom the Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom.
Marc DaigneaultFrom the Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom.
Amanda BurnettFrom the Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom.
Victoria RidgerFrom the Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom.
Janet ChamberlainFrom the Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom.
Sheila FrancisFrom the Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom s.francis@sheffield.ac.uk.
University of Sheffield · GB

Funding

British Heart Foundation PG/11/85/29147British Heart Foundation PG/14/38/30862
6 · The paper itself

Abstract

The endothelium is critically involved in the pathogenesis of atherosclerosis by producing pro-inflammatory mediators, including IL-1β. Coronary arteries from patients with ischemic heart disease express large amounts of IL-1β in the endothelium. However, the mechanism by which endothelial cells (ECs) release IL-1β remains to be elucidated. We investigated neutrophil elastase (NE), a potent serine protease detected in vulnerable areas of human carotid plaques, as a potential "trigger" for IL-1β processing and release. This study tested the hypothesis that NE potentiates the processing and release of IL-1β from human coronary endothelium. We found that NE cleaves the pro-isoform of IL-1β in ECs and causes significant secretion of bioactive IL-1β via extracellular vesicles. This release was attenuated significantly by inhibition of neutrophil elastase but not caspase-1. Transient increases in intracellular Ca(2+) levels were observed prior to secretion. Inside ECs, and after NE treatment only, IL-1β was detected within LAMP-1-positive multivesicular bodies. The released vesicles contained bioactive IL-1β. In vivo, in experimental atherosclerosis, NE was detected in mature atherosclerotic plaques, predominantly in the endothelium, alongside IL-1β. This study reveals a novel mechanistic link between NE expression in atherosclerotic plaques and concomitant pro-inflammatory bioactive IL-1β secretion from ECs. This could reveal additional potential anti-IL-1β therapeutic targets and provide further insights into the inflammatory process by which vascular disease develops.

Indexed as

Gene Expression Regulation, EnzymologicAnimalsApolipoproteins EApoptosisCalciumCells, CulturedCell SurvivalCoronary VesselsEndothelial CellsEndothelium, VascularHumansImmunohistochemistryInflammationInterleukin-1betaLeukocyte ElastaseMaleApolipoproteins ECalciumIL1B protein, humanIL1B protein, mouseInterleukin-1betaLeukocyte Elastaseatherosclerosisendotheliumextracellular vesiclesIL-1inflammationneutrophil elastase

Identifiers

PMID26269588
PMCPMC4591798
OpenAlexW2118763861

What OpenQuestion holds

Textmetadata
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.