Evidence map›Paper›PMID 25941817›Full record

ArticleCurrent molecular medicine2015

Celastrol inhibits inflammatory stimuli-induced neutrophil extracellular trap formation.

Y Yu, C D Koehn, Y Yue, S Li, G M Thiele, M P Hearth-Holmes, T R Mikuls, J R O'Dell, L W Klassen, Z Zhang and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Current molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 10% 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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.

  1. Pooled it
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  15. Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by altering macrophage polarization via the miR-449a/NLRP3 axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021
    Article
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  17. Frontiers in pharmacology · 2021
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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

11 authors at 3 institutions in 1 country.

Y Yu
C D Koehn
Y Yue
S Li
G M Thiele
M P Hearth-Holmes
T R Mikuls
J R O'Dell
L W Klassen
Z Zhang
K SuDepartment of Pathology and Microbiology, University of Nebraska Medical Center, LTC 11724, 987660 Nebraska Medical Center, Omaha, NE 68198- 7660, USA. ksu@unmc.edu.
University of Nebraska Medical Center · USVA Nebraska Western Iowa Health Care System · USFred and Pamela Buffett Cancer Center

Funding

Novel Neutrophil Autoantigens in Systemic Lupus ErythematosusR01AR059351 · NIAMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SU, KAIHONG · 2011 to 2015
$1.5M
NIAMS NIH HHS R01 AR059351
6 · The paper itself

Abstract

Neutrophil extracellular traps (NETs) are web-like structures released by activated neutrophils. Recent studies suggest that NETs play an active role in driving autoimmunity and tissue injury in diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The purpose of this study was to investigate if celastrol, a triterpenoid compound, can inhibit NET formation induced by inflammatory stimuli associated with RA and SLE. We found that celastrol can completely inhibit neutrophil oxidative burst and NET formation induced by tumor necrosis factor alpha (TNFα) with an IC50 of 0.34 µM and by ovalbumin:anti-ovalbumin immune complexes (Ova IC) with an IC50 of 1.53 µM. Celastrol also completely inhibited neutrophil oxidative burst and NET formation induced by immunoglobulin G (IgG) purified from RA and SLE patient sera. Further investigating into the mechanisms, we found that celastrol treatment downregulated the activation of spleen tyrosine kinase (SYK) and the concomitant phosphorylation of mitogen-activated protein kinase kinase (MAPKK/MEK), extracellular-signal-regulated kinase (ERK), and NFκB inhibitor alpha (IκBα), as well as citrullination of histones. Our data reveals that celastrol potently inhibits neutrophil oxidative burst and NET formation induced by different inflammatory stimuli, possibly through downregulating the SYK-MEK-ERK-NFκB signaling cascade. These results suggest that celastrol may have therapeutic potentials for the treatment of inflammatory and autoimmune diseases involving neutrophils and NETs.

Indexed as

Arthritis, RheumatoidCells, CulturedEnzyme ActivationExtracellular Signal-Regulated MAP KinasesExtracellular TrapsHumansI-kappa B ProteinsImmunoglobulin GInflammationIntracellular Signaling Peptides and ProteinsLupus Erythematosus, SystemicMAP Kinase Kinase KinasesNeutrophilsNF-KappaB Inhibitor alphaOvalbuminPentacyclic TriterpenescelastrolExtracellular Signal-Regulated MAP KinasesI-kappa B ProteinsImmunoglobulin GIntracellular Signaling Peptides and ProteinsMAP Kinase Kinase KinasesNF-KappaB Inhibitor alphaNFKBIA protein, humanOvalbuminPentacyclic TriterpenesProtein-Tyrosine KinasesSyk KinaseSYK protein, humanTriterpenesTumor Necrosis Factor-alpha

Identifiers

PMID25941817
PMCPMC4527119
OpenAlexW2168977519

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.