Hypoxia augments cytokine (transforming growth factor-beta (TGF-β) and IL-1)-induced vascular endothelial growth factor secretion by human synovial fibroblasts
| Autor: | F. Brown, J. A. Hunt, Roy A. Fava, R. J. Diegel, P. Morganelli, B. Berse, K.-T. Yeo |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Angiogenesis medicine.medical_treatment Immunology Basic fibroblast growth factor Endothelial Growth Factors Biology chemistry.chemical_compound Transforming Growth Factor beta Internal medicine medicine Humans Protein Isoforms Immunology and Allergy RNA Messenger Hypoxia Lymphokines Dose-Response Relationship Drug Vascular Endothelial Growth Factors Arthritis Growth factor Synovial Membrane Original Articles Fibroblasts Blotting Northern Vascular endothelial growth factor Vascular endothelial growth factor A Endocrinology medicine.anatomical_structure Cytokine chemistry biology.protein Cytokines Synovial membrane Platelet-derived growth factor receptor Interleukin-1 |
| Zdroj: | Clinical and Experimental Immunology. 115:176-182 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1046/j.1365-2249.1999.00775.x |
| Popis: | SUMMARYVascular endothelial growth factor (VEGF) is abundant in synovium and synovial fluids, where it probably contributes to vascular permeability and angiogenesis in arthritic joints. To investigate the probable sources of VEGF in synovium, we compared the ability of several cytokines (TGF-β, platelet-derived growth factor (PDGF), IL-1, tumour necrosis factor (TNF), basic fibroblast growth factor (bFGF) that are associated with arthritis and angiogenesis, to stimulate secretion of VEGF protein by human synovial fibroblasts. TGF-β was the strongest inducer of VEGF secretion; six times more VEGF was secreted when cells were stimulated by TGF-β than when stimulated by PDGF or IL-1 for 24 h. TNF-α and bFGF did not stimulate any secretion of VEGF. The stimulatory effects of TGF-β and IL-1 on VEGF secretion were additive. Hypoxic culture alone also stimulated VEGF secretion, but more importantly, hypoxic culture conditions doubled the rate of VEGF secretion stimulated by the cytokines TGF-β and IL-1. When dermal and synovial fibroblasts were stimulated identically by hypoxia and cytokines (TGF-β and IL-1), synovial fibroblasts secreted four times more VEGF than did dermal fibroblasts. Thus in rheumatoid arthritis, the capacity of synovial fibroblasts in the hypoxic environment to secrete large amounts of VEGF in response to cytokines such as TGF-β probably contributes significantly to angiogenesis in the synovium. |
| Databáze: | OpenAIRE |
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