Evidence map›Paper›PMID 26696093›Full record

Trial reportRespiratory research2015

Regulation of YKL-40 expression by corticosteroids: effect on pro-inflammatory macrophages in vitro and its modulation in COPD in vivo.

L I Z Kunz, E F A van't Wout, A van Schadewijk, D S Postma, H A M Kerstjens, P J Sterk, P S Hiemstra

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Respiratory research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00158847 (Modification of Disease Outcome in COPD. Shortterm Versus Longterm Treatment With Inhaled Corticosteroids, Either or Not Combined With a Long-Acting Beta2-Agonist.), which is not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.6field-weighted citation impact, top 30% 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.

NCT00158847 phase4terminatednot on this map

Modification of Disease Outcome in COPD. Shortterm Versus Longterm Treatment With Inhaled Corticosteroids, Either or Not Combined With a Long-Acting Beta2-Agonist.

TypeinterventionalSponsorLeiden University Medical CenterRan2000 to 2005Enrolled200ConditionsChronic Obstructive Pulmonary DiseaseArmsfluticasone 500 mcg, fluticasone 500 mcg + salmeterol 50 mcg
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. [YKL-40 Promotes the Expression of Inflammatory Factors in Type Ⅱ Alveolar Epithelial Cell Model of A549 Cell Line].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. 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 4 institutions in 1 country.

L I Z KunzDepartment of Pulmonology, Leiden University Medical Center, Albinusdreef 2, NL-2333, ZA, Leiden, The Netherlands. L.I.Z.Kunz@lumc.nl.
E F A van't WoutDepartment of Pulmonology, Leiden University Medical Center, Albinusdreef 2, NL-2333, ZA, Leiden, The Netherlands. E.F.A.van_t_Wout@lumc.nl.
A van SchadewijkDepartment of Pulmonology, Leiden University Medical Center, Albinusdreef 2, NL-2333, ZA, Leiden, The Netherlands. A.van_Schadewijk@lumc.nl.
D S PostmaDepartment of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. D.S.Postma@umcg.nl.
H A M KerstjensDepartment of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. H.A.M.Kerstjens@umcg.nl.
P J SterkDepartment of Respiratory Medicine, Academic Medical Center, Amsterdam, The Netherlands. P.J.Sterk@amc.nl.
P S HiemstraDepartment of Pulmonology, Leiden University Medical Center, Albinusdreef 2, NL-2333, ZA, Leiden, The Netherlands. P.S.Hiemstra@lumc.nl.
Leiden University Medical Center · NLAcademic Medical Center · NLUniversity Medical Center Groningen · NLUniversity of Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMacrophages constitute a heterogeneous cell population with pro- (MΦ1) and anti-inflammatory (MΦ2) cells. The soluble chitinase-like-protein YKL-40 is expressed in macrophages and various other cell types, and has been linked to a variety of inflammatory diseases, including COPD. Dexamethasone strongly reduces YKL-40 expression in peripheral blood mononuclear cells (PBMC) in vitro. We hypothesized that: a) YKL-40 is differentially expressed by MΦ1 and MΦ2, b) is decreased by corticosteroids and c) that long-term treatment with inhaled corticosteroids (ICS) affects YKL-40 levels in serum and sputum of COPD patients.

methodsMonocytes of healthy subjects were cultured in vitro for 7 days with either GM-CSF or M-CSF (for MΦ1 and MΦ2, respectively) and stimulated for 24 h with LPS, TNFα, or oncostatin M (OSM). MΦ1 and MΦ2 differentiation was assessed by measuring secretion of IL-12p40 and IL-10, respectively. YKL-40 expression in macrophages was measured by quantitative RT-PCR (qPCR) and ELISA; serum and sputum YKL-40 levels were analyzed by ELISA.

resultsPro-inflammatory MΦ1 cells secreted significantly more YKL-40 than MΦ2, which was independent of stimulation with LPS, TNFα or OSM (p < 0.001) and confirmed by qPCR. Dexamethasone dose-dependently and significantly inhibited YKL-40 protein and mRNA levels in MΦ1. Serum YKL-40 levels of COPD patients were significantly higher than sputum YKL-40 levels but were not significantly changed by ICS treatment.

conclusionsYKL-40 secretion from MΦ1 cells is higher than from MΦ2 cells and is unaffected by further stimulation with pro-inflammatory agents. Furthermore, YKL-40 release from cultured monocyte-derived macrophages is inhibited by dexamethasone especially in MΦ1, but ICS treatment did not change YKL-40 serum and sputum levels in COPD. These results indicate that YKL-40 expression could be used as a marker for MΦ1 macrophages in vitro, but not for monitoring the effect of ICS in COPD.

trial registrationClinicalTrials.gov, registration number: NCT00158847.

Indexed as

AdipokinesAdministration, InhalationAgedAnti-Inflammatory AgentsBiomarkersBronchodilator AgentsCells, CulturedChitinase-3-Like Protein 1DexamethasoneDose-Response Relationship, DrugDown-RegulationDrug Administration ScheduleFemaleFluticasone-Salmeterol Drug CombinationGlucocorticoidsHumansAdipokinesAnti-Inflammatory AgentsBiomarkersBronchodilator AgentsCHI3L1 protein, humanChitinase-3-Like Protein 1DexamethasoneFluticasone-Salmeterol Drug CombinationGlucocorticoidsInflammation MediatorsLectins

Identifiers

PMID26696093
PMCPMC4699377
OpenAlexW2206968316

What OpenQuestion holds

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LicenceCC BY
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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.