Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0004153 (
atherosclerosis
)
77,401
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
YKL-39
is a Glyco_18 domain containing chitinase-like protein which is currently recognized as a biomarker for the activation of chondrocytes and the progress of the osteoarthritis in human.
YKL-39
was identified as an abundantly secreted protein in primary culture of human articular chondrocytes. Two biological activities of
YKL-39
might contribute to the disease progression. One is the induction of autoimmune response and second is the participation in tissue remodeling. Other mammalian chitinase-like proteins including chitotriosidase, SI-CLP, YKL-40 and YM1 are expressed by macrophages in various pathological conditions. In contrast,
YKL-39
was never reported to be produced by macrophages. We used in vitro model of human monocyte-derived macrophage differentiation to analyse regulation of
YKL-39
expression. Expression of
YKL-39
was examined by real-time RT-PCR. CD14+ MACS sorted human monocytes differentiated for 6 days under different stimulations including IFNgamma, IL-4, dexamethasone and TGF-beta. We found that both IL-4 and TGF-beta have weak stimulatory effect on
YKL-39
expression in all donors tested (3.2 +/- 1.7 fold, p = 0.006 and 6.3 +/- 3.1 fold, p = 0.014 respectively). However the combination of IL-4 and TGF-beta had strong stimulatory effect on the expression of
YKL-39
in all analysed individual macrophage cultures (34 +/- 36 fold, p = 0.05). IFN-gamma did not show statistically significant effect of
YKL-39
mRNA expression. Presence of dexamethasone almost completely abolished the stimulatory effects of IL-4 and TGF-beta. In summary, we show here for the first time, that human cells of monocyte origin are able to produce
YKL-39
. Maturation of monocyte derived macrophages in the presence of Th2 cytokine IL-4 and TGF-beta leads to the strong activation of
YKL-39
expression. Thus elevated levels of
YKL-39
observed during chronic inflammations can not be attributed solely to the activity of chondrocytes. In perspective,
YKL-39
might serve as a useful biomarker to detect macrophage-specific response in pathologies like tumour,
atherosclerosis
and Alzheimer disease.
...
PMID:Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages. 1957 92
