| Title |
Regulation of YKL-40 expression by corticosteroids: effect on pro-inflammatory macrophages in vitro and its modulation in COPD in vivo
|
|---|---|
| Published in |
Respiratory Research, December 2015
|
| DOI | 10.1186/s12931-015-0314-3 |
| Pubmed ID | |
| Authors |
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 |
| Abstract |
Macrophages 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. Monocytes 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. Pro-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. YKL-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. ClinicalTrials.gov, registration number: NCT00158847. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 67% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 47 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 10 | 21% |
| Student > Ph. D. Student | 7 | 15% |
| Researcher | 5 | 11% |
| Student > Bachelor | 4 | 9% |
| Professor | 4 | 9% |
| Other | 8 | 17% |
| Unknown | 9 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 28% |
| Biochemistry, Genetics and Molecular Biology | 8 | 17% |
| Agricultural and Biological Sciences | 5 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 9% |
| Immunology and Microbiology | 2 | 4% |
| Other | 4 | 9% |
| Unknown | 11 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 April 2023.
All research outputs
#14,915,133
of 25,374,647 outputs
Outputs from Respiratory Research
#1,499
of 3,062 outputs
Outputs of similar age
#195,961
of 396,428 outputs
Outputs of similar age from Respiratory Research
#19
of 33 outputs
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