Induction of Bone-Type Alkaline Phosphatase in Human Vascular Smooth Muscle Cells
| Autor: | Atsushi Shioi, Hidenori Koyama, Yasuhisa Okuno, Yoshiki Nishizawa, Katsuhito Mori, Shuichi Jono, Miwako Katagi |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Physiology Sialoglycoproteins medicine.medical_treatment Receptors Cytoplasmic and Nuclear Oncostatin M Bone and Bones Gene Expression Regulation Enzymologic Monocytes Muscle Smooth Vascular Receptors Tumor Necrosis Factor Cell Line Interferon-gamma Internal medicine medicine Humans Macrophage Osteopontin Glycoproteins Dose-Response Relationship Drug biology Tumor Necrosis Factor-alpha Macrophages Monocyte Osteoprotegerin Alkaline Phosphatase medicine.disease Molecular biology Coculture Techniques Endocrinology Cytokine medicine.anatomical_structure Culture Media Conditioned Enzyme Induction Steroid Hydroxylases biology.protein Calcium Tumor necrosis factor alpha Peptides Cardiology and Cardiovascular Medicine Calcification |
| Zdroj: | Circulation Research. 91:9-16 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000026421.61398.f2 |
| Popis: | Inflammatory cells such as macrophages and T lymphocytes play an important role in vascular calcification associated with atherosclerosis and cardiac valvular disease. In particular, macrophages activated with cytokines derived from T lymphocytes such as interferon-γ (IFN-γ) may contribute to the development of vascular calcification. Moreover, we have shown the stimulatory effect of 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) on in vitro calcification through increasing the expression of alkaline phosphatase (ALP), an ectoenzyme indispensable for bone mineralization, in vascular smooth muscle cells. Therefore, we hypothesized that macrophages may induce calcifying phenotype, especially the expression of ALP in human vascular smooth muscle cells (HVSMCs) in the presence of IFN-γ and 1,25(OH) 2 D 3 . To test this hypothesis, we used cocultures of HVSMCs with human monocytic cell line (THP-1) or peripheral blood monocytes (PBMCs) in the presence of IFN-γ and 1,25(OH) 2 D 3 . THP-1 cells or PBMCs induced ALP activity and its gene expression in HVSMCs and the cells with high expression of ALP calcified their extracellular matrix by the addition of β-glycerophosphate. Thermostability and immunoassay showed that ALP induced in HVSMCs was bone-specific enzyme. We further identified tumor necrosis factor-α (TNF-α) and oncostatin M (OSM) as major factors inducing ALP in HVSMCs in the culture supernatants of THP-1 cells. TNF-α and OSM, only when applied together, increased ALP activities and in vitro calcification in HVSMCs in the presence of IFN-γ and 1,25(OH) 2 D 3 . These results suggest that macrophages may contribute to the development of vascular calcification through producing various inflammatory mediators, especially TNF-α and OSM. |
| Databáze: | OpenAIRE |
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