Induction and Expression of Human Cartilage Glycoprotein 39 in Rheumatoid Inflammatory and Peripheral Blood Monocyte-Derived Macrophages

doi:10.1006/excr.1997.3764

Experimental Cell Research

Volume 237, Issue 1, 25 November 1997, Pages 46-54

https://doi.org/10.1006/excr.1997.3764 Get rights and content

Abstract

Human cartilage glycoprotein 39 (HC gp-39) has been described as a major secreted product of cultured articular chondrocytes, synovial fibroblasts, and the osteosarcoma line MG63. However, its expression in these cells types has not been directly linked to corresponding cell typesin vivo.In this report, expression of HC gp-39 is demonstrated from peripheral blood-derived macrophages in association with their differentiation from monocytes to macrophages. Consistent with macrophage specificity, HC gp-39 expression is also induced upon selective stimulation of the pluripotent promyelocytic leukemia cell line HL-60 toward the monocyte/macrophage lineage with vitamin D₃or phorbol 12-myristate 13-acetate (PMA), while treatments stimulating granulocyte and eosinophilic pathways do not induce expression. Furthermore, HC gp-39 expression levels correlate with the degree of morphological differentiation induced by PMA and vitamin D₃treatments. PMA-induced mRNA expression occurs by 36 h and is a secondary transcriptional response since its synthesis is inhibited by cycloheximide. Apparently, HC gp-39 expression is tied to later events in the differentiation of monocytes into macrophages. Thein vivosignificance of these results is validated by thein situdetection of HC gp-39 mRNA in inflammatory macrophages associated with rheumatoid synovium. Thus, macrophages appear to be an important source of HC gp-39, which has been shown to be present at elevated levels in the blood and synovium of rheumatoid arthritis patients. The implications of this extend well beyond the previously restricted observations in cell types associated with the joint and suggest a potential involvement of macrophage-derived HC gp-39 in other aspects of inflammation, tissue remodeling, and host defense.

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Citation Excerpt :
Human cartilage glycoprotein 39 (HC-gp39), or YKL-40, is a recently identified inflammatory protein that belongs to the glycosyl hydrolases family 18. YKL-40 represents a major secreted product of activated macrophages, neutrophils, vascular smooth muscle cells, chondrocytes, synoviocytes and tumor cells (Johansen, 2006; Kirkpatrick et al., 1997; Rehli et al., 2003). However, its function remains unclear.
This study aims to investigate rat hippocampal cartilage glycoprotein-39 (YKL-40) expression levels following status epilepticus (SE), and the potential mechanism of YKL-40 in SE-induced neuronal injury.
Seventy-two healthy adult male Sprague-Dawley rats were randomly assigned into two groups: control and SE groups. A lithium chloride-pilocarpine SE model was established, and the control group was injected with sodium chloride. The hippocampus was assessed at three, six, 12, 24 and 72 h after SE. YKL-40 protein was detected via immunohistochemistry (n = 6). Cellular YKL-40/neuronal nuclei antigen (NeuN) expression levels were determined with double immunofluorescence. YKL-40 mRNA was detected via quantitative real-time polymerase chain reaction (qRT-PCR, n = 6).
YKL-40 immunoreactivity was poor and was mainly localized to the cytoplasm within hippocampal CA3/CA4 neurons with limited immunoreactivity in the nucleus in the control group. Following SE, YKL-40 immunoreactivity exhibited a diffused distribution throughout the cytoplasm in neurons and increased distribution in the nucleus. CA3 and CA4 YKL-40 protein expression significantly increased at six hours post-SE (P < 0.05), peaked at 12 h (P < 0.01), and decreased at 24 h (P < 0.05) and 72 h (P < 0.05) in the SE group, compared with the control group. Double-label immunofluorescence of YKL-40/NeuN exhibited a hippocampal CA3/CA4 neuron location. Furthermore, SE induced a significant increase inYKL-40 mRNA at six, 24, or 72 h (P < 0.05); which peaked at 12 h (P < 0.01).
YKL-40 was expressed in neurons, and elevated rat hippocampal YKL-40 expression levels may be involved in the pathogenesis of injury following SE.
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Only chitotriosidase (CHIT-1) and acidic mammalian chitinase (AMCase) have demonstrated a chitinolytic activity, while chitinase-like proteins can bind chitin, but do not have chitinolytic activity [1]. CHI3L1 is produced by a variety of cells including chondrocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, hepatic stellate cells, airway epithelial cells, neutrophils, inflammatory macrophages and different types of cancer cells [2–9]. Regarding the central nervous system (CNS), its expression has also been described in astrocytes and microglia of encephalitic monkeys and human immunodeficiency virus encephalitis patients as well as in samples of human brain infarction [10,11].
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¹: To whom correspondence and reprint requests should be addressed at Department of Gene Expression Sciences, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406. Fax: (610) 270-5093.

²: Current address: Division of Anti-infectives, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426.

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Regular ArticleInduction and Expression of Human Cartilage Glycoprotein 39 in Rheumatoid Inflammatory and Peripheral Blood Monocyte-Derived Macrophages

Abstract

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Gene

J. Biol. Chem.

J. Biol. Chem.

Blood

Leukocyte Res.

J. Biol. Chem.

J. Biol. Chem.

Eur. J. Cancer A

Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period

Biochem. J.

Identification of proteins secreted by human osteoblastic cells in culture

J. Bone Miner. Res.

Regular Article
Induction and Expression of Human Cartilage Glycoprotein 39 in Rheumatoid Inflammatory and Peripheral Blood Monocyte-Derived Macrophages