Circulating chromogranin A reveals extra-articular involvement in patients with rheumatoid arthritis and curbs TNF-α-elicited endothelial activation
| Autor: | Reinhard E. Voll, Ruediger B Mueller, Alessandro Marinosci, Carlo Maria Rossi, Elena Baldissera, Gabriele Di Comite, Angelo Corti, Karine Lolmede, Maria Grazia Sabbadini, Angelo A. Manfredi, Martin Herrmann, Patrizia Rovere-Querini, Patrizia Aiello |
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| Přispěvatelé: | Di Comite, G, Rossi, Cm, Marinosci, A, Lolmede, K, Baldissera, E, Aiello, P, Mueller, Rb, Herrmann, M, Voll, Re, ROVERE QUERINI, Patrizia, Sabbadini, Mg, Corti, Angelo, Manfredi, ANGELO ANDREA M. A. |
| Rok vydání: | 2008 |
| Předmět: |
Male
Vasculitis endocrine system medicine.medical_specialty Endothelium Pulmonary Fibrosis Immunology Arthritis CCL2 Arthritis Rheumatoid Endothelial activation Internal medicine Humans Immunology and Allergy Medicine Prospective Studies Cells Cultured Chemokine CCL2 Autoantibodies Feedback Physiological Serositis biology Tumor Necrosis Factor-alpha business.industry Synovial Membrane Endothelial Cells Peripheral Nervous System Diseases Chromogranin A Cell Biology Middle Aged Intercellular Adhesion Molecule-1 medicine.disease medicine.anatomical_structure Endocrinology Rheumatoid arthritis Microvessels Rheumatoid vasculitis biology.protein Female Endothelium Vascular Inflammation Mediators business Cell activation Biomarkers |
| Zdroj: | Journal of Leukocyte Biology. 85:81-87 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.0608358 |
| Popis: | TNF-α plays an important role in the natural history of rheumatoid arthritis (RA), a systemic disease characterized by endothelial activation and synovial involvement with bone erosions. Neuroendocrine signals contribute as well to RA, but their role is poorly understood. We measured in 104 RA patients and in an equal number of sex- and age-matched, healthy controls the blood levels of chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF-α-mediated vascular inflammation. CgA levels were significantly higher in patients with RA and remained stable over time. High levels of CgA were significantly associated with severe extra-articular manifestations, namely pulmonary fibrosis, rheumatoid vasculitis, serositis, and peripheral neuropathy. RA sera curbed the response of human microvascular endothelial cells to TNF-α, as assessed by the expression of ICAM-1, the release of MCP-1/CCL2, and the export of nuclear high-mobility group box 1; the effect abated in the presence of anti-CgA antibodies. The efficacy of the blockade was significantly correlated with the CgA concentration in the serum. The recombinant aminoterminal portion of CgA, corresponding to residues 1–78, had similar inhibitory effects on endothelial cells challenged with TNF-α. Our results suggest that enhanced levels of CgA identify patients with extra-articular involvement and reveal a negative feedback loop that limits the activation of endothelial cells in RA. |
| Databáze: | OpenAIRE |
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