Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages
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. T...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2008-01-01
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| Series: | Biomarker Insights |
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| Online Access: | http://la-press.com/article.php?article_id=560 |
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| author | Julia Kzhyshkowska Sergij Goerdt LiMing Gooi Christina Schmuttermaier Srinivas Mamidi Alexei Gratchev |
| author_facet | Julia Kzhyshkowska Sergij Goerdt LiMing Gooi Christina Schmuttermaier Srinivas Mamidi Alexei Gratchev |
| author_sort | Julia Kzhyshkowska |
| collection | DOAJ |
| description | 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 IFNγ, IL-4, dexamethasone and TGF-β. We found that both IL-4 and TGF-β 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-β had strong stimulatory effect on the expression of YKL-39 in all analysed individual macrophage cultures (34 ± 36 fold, p = 0.05). IFN-γ 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-β. 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-β 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, |
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| institution | Directory Open Access Journal |
| issn | 1177-2719 |
| language | English |
| last_indexed | 2024-12-24T03:21:58Z |
| publishDate | 2008-01-01 |
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| spelling | doaj.art-74ad55ddf22c4ff1bd6f4f1e43ac95b22022-12-21T17:17:27ZengSAGE PublishingBiomarker Insights1177-27192008-01-0133944Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating MacrophagesJulia KzhyshkowskaSergij GoerdtLiMing GooiChristina SchmuttermaierSrinivas MamidiAlexei GratchevYKL-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 IFNγ, IL-4, dexamethasone and TGF-β. We found that both IL-4 and TGF-β 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-β had strong stimulatory effect on the expression of YKL-39 in all analysed individual macrophage cultures (34 ± 36 fold, p = 0.05). IFN-γ 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-β. 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-β 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,http://la-press.com/article.php?article_id=560osteoarthritischitinaseYKL-39macrophageTGF-betaIL-4 |
| spellingShingle | Julia Kzhyshkowska Sergij Goerdt LiMing Gooi Christina Schmuttermaier Srinivas Mamidi Alexei Gratchev Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages Biomarker Insights osteoarthritis chitinase YKL-39 macrophage TGF-beta IL-4 |
| title | Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages |
| title_full | Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages |
| title_fullStr | Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages |
| title_full_unstemmed | Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages |
| title_short | Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages |
| title_sort | expression of osteoarthritis marker ykl 39 is stimulated by transforming growth factor beta tgf beta and il 4 in differentiating macrophages |
| topic | osteoarthritis chitinase YKL-39 macrophage TGF-beta IL-4 |
| url | http://la-press.com/article.php?article_id=560 |
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