Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): specific up-regulation by tumour necrosis factor-alpha (TNF-α) in synovial fluid
| Autor: | Martyn J. Bottomley, N. J. A. Webb, P. J. L. Holt, P. E. C. Brenchley, Anthony J. Freemont, C. J. Watson |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Lipopolysaccharides
Vascular Endothelial Growth Factor A medicine.medical_specialty medicine.medical_treatment Immunology Arthritis Endothelial Growth Factors Lymphocyte Activation Peripheral blood mononuclear cell Autoimmune Diseases Arthritis Rheumatoid chemistry.chemical_compound Internal medicine Synovial Fluid medicine Humans Immunology and Allergy Synovial fluid Lymphokines Tumor Necrosis Factor-alpha Vascular Endothelial Growth Factors business.industry Interleukins Monocyte Lymphokine medicine.disease Vascular endothelial growth factor Endocrinology medicine.anatomical_structure Cytokine chemistry Leukocytes Mononuclear Original Article Tumor necrosis factor alpha business |
| Zdroj: | Clinical and Experimental Immunology. 117:171-176 |
| ISSN: | 1365-2249 0009-9104 |
| Popis: | SUMMARYThis study was designed to investigate VEGF production from peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) compared with healthy controls and to identify the predominant cellular source in PBMC isolated from RA patients. The regulation of PBMC VEGF production by cytokines and synovial fluid (SF) was studied. PBMC were isolated from RA patients and healthy controls and stimulated with lipopolysaccharide (LPS), IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α and transforming growth factor-beta (TGF-β) isoforms for varying time points up to 72 h at 37°C/5% CO2. The effect of SF on VEGF secretion by PBMC was also studied. Supernatant VEGF levels were measured using a flt-1 receptor capture ELISA. RA patients had significantly higher spontaneous production of VEGF compared with controls, and monocytes were identified as the predominant cellular source. RA PBMC VEGF production was up-regulated by TGF-β isoforms and TNF-α and down-regulated by IL-4 and IL-10, with no effect observed with IL-1β, IL-6 and IL-8. Antibody blocking experiments confirmed that TNF-α and not TGF-β isoforms in SF increased VEGF secretion by RA PBMC. These results emphasize the importance of monocytes as a source of VEGF in the pathophysiology of RA. Several cytokines known to be present in SF can modulate the level of VEGF secretion, but the predominant effect of SF in VEGF up-regulation is shown to be dependent on TNF-α. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|