Evidence map›Paper›PMID 20668705›Full record

ArticlePloS one2010

Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation.

Kristiina Rajamäki, Jani Lappalainen, Katariina Oörni, Elina Välimäki, Sampsa Matikainen, Petri T Kovanen, Kari K Eklund

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03726645 (The Role of Gut Microbiota in the Pathogenesis of Ankylosing Spondylitis), which is not on this map. Cited by 509 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
509citing papers in PubMed, 1 pooled it
22.7field-weighted citation impact, top 1% 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.

NCT03726645 early_phase1unknown statusnot on this mapstarted 2018, after this paper: background citation

The Role of Gut Microbiota in the Pathogenesis of Ankylosing Spondylitis (AS), and the Effect of Fecal Microbiota Transplantation on Gut Microbiota, Gut Wall Inflammation and Clinical Activity of AS

TypeinterventionalSponsorHospital District of Helsinki and UusimaaRan2018 to 2020Enrolled20ConditionsAnkylosing SpondylitisArmsFecal microbiota transplantation
3 · Its place in the literature

Who cites it

509 citing papers in PubMed, 1 synthesis or guideline pooled it, 996 citations in OpenAlex.

  1. Pooled it
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  9. Altered cholesterol immunometabolism activates the macrophage NLRP3-inflammasome in lung fibrosis.American journal of respiratory cell and molecular biology · 2026
    Article
  10. Article
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  12. PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026
    Review
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  15. Article
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449 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

7 authors at 2 institutions in 1 country.

Kristiina RajamäkiWihuri Research Institute, Helsinki, Finland. kristiina.rajamaki@helsinki.fi
Jani Lappalainen
Katariina Oörni
Elina Välimäki
Sampsa Matikainen
Petri T Kovanen
Kari K Eklund
Wihuri Research Institute · FIFinnish Institute of Occupational Health · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic inflammation of the arterial wall is a key element in the pathogenesis of atherosclerosis, yet the factors that trigger and sustain the inflammation remain elusive. Inflammasomes are cytoplasmic caspase-1-activating protein complexes that promote maturation and secretion of the proinflammatory cytokines interleukin(IL)-1beta and IL-18. The most intensively studied inflammasome, NLRP3 inflammasome, is activated by diverse substances, including crystalline and particulate materials. As cholesterol crystals are abundant in atherosclerotic lesions, and IL-1beta has been linked to atherogenesis, we explored the possibility that cholesterol crystals promote inflammation by activating the inflammasome pathway. PRINCIPAL

findingsHere we show that human macrophages avidly phagocytose cholesterol crystals and store the ingested cholesterol as cholesteryl esters. Importantly, cholesterol crystals induced dose-dependent secretion of mature IL-1beta from human monocytes and macrophages. The cholesterol crystal-induced secretion of IL-1beta was caspase-1-dependent, suggesting the involvement of an inflammasome-mediated pathway. Silencing of the NLRP3 receptor, the crucial component in NLRP3 inflammasome, completely abolished crystal-induced IL-1beta secretion, thus identifying NLRP3 inflammasome as the cholesterol crystal-responsive element in macrophages. The crystals were shown to induce leakage of the lysosomal protease cathepsin B into the cytoplasm and inhibition of this enzyme reduced cholesterol crystal-induced IL-1beta secretion, suggesting that NLRP3 inflammasome activation occurred via lysosomal destabilization.

conclusionsThe cholesterol crystal-induced inflammasome activation in macrophages may represent an important link between cholesterol metabolism and inflammation in atherosclerotic lesions.

Indexed as

Blotting, WesternCarrier ProteinsCaspase 1Caspase InhibitorsCathepsin BCells, CulturedCholesterolChromatography, Thin LayerCytochalasin DCytoplasmHumansInflammationInterleukin-1betaLipopolysaccharidesLysosomesMacrophagesCarrier ProteinsCaspase 1Caspase InhibitorsCathepsin BCholesterolCytochalasin DInterleukin-1betaLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanPotassiumRNA, Small Interfering

Identifiers

PMID20668705
PMCPMC2909263
OpenAlexW2028545985

What OpenQuestion holds

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Registered trials

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.