Interferon-β and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling
| Autor: | Kozaburo Hayashi, M. T. Lee, R. B. Nussenblatt, L.C. Hooper, Barbara Detrick, Leila I. Kump, John J. Hooks |
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| Rok vydání: | 2006 |
| Předmět: |
Lipopolysaccharides
Pathology medicine.medical_specialty Interferon Inducers medicine.medical_treatment Immunology Gene Expression Behcet's disease Uveitis Interferon-gamma chemistry.chemical_compound Clinical Studies E-selectin medicine Humans Immunology and Allergy Cells Cultured RNA Double-Stranded Retinal Vasculitis biology Tumor Necrosis Factor-alpha Retinal vasculitis Cell adhesion molecule business.industry Behcet Syndrome Antibodies Monoclonal Endothelial Cells Interferon-alpha Retinal Interferon-beta Intercellular Adhesion Molecule-1 medicine.disease Toll-Like Receptor 3 Poly I-C Cytokine chemistry Case-Control Studies Acute Disease biology.protein Endothelium Vascular E-Selectin business Vasculitis Signal Transduction |
| Zdroj: | Clinical and Experimental Immunology. 147:71-80 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.2006.03253.x |
| Popis: | Summary Retinal vasculitis is a major component of ocular inflammation that plays a role in retinal tissue damage in patients with idiopathic uveitis and Behçet's disease. Here we show that type 1 interferons (IFN α/β) were not detected in sera from normal individuals but were identified in up to 46% of the sera from retinal vasculitis patients. The predominant form of IFN observed was IFN-β, which was detected in 39% of Behçet's disease patients and 47% of idiopathic uveitis patients. Seven patients whose sera contained IFN-β were monitored prospectively. IFN-β was shown to be present for 6–12 months in all seven of the sera samples tested. Furthermore, the adhesion molecule profile identified in this study was strikingly different when Behçet's and uveitis patient sera were compared to sera from normal controls. Sera from Behçet's disease patients contained significantly elevated levels of the soluble adhesion molecules, sE-selectin and s-intracellular adhesion molecule-1 (sICAM-1), whereas sera from patients with idiopathic uveitis contained significantly increased sE-selectin. In vitro studies evaluating the cell source of these cytokines revealed that polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular endothelial cells produce sE-selectin, sICAM-1 and IFN-β. Production of these molecules was inhibited by pretreatment with anti-Toll-like receptor 3 (TLR-3) antibody. In conclusion, IFN-β, sE-selectin and sICAM-1 are elevated in patients with retinal vasculitis and are induced in retinal vascular endothelial cells in vitro by activating the innate immune system through TLR-3. Further analysis of innate immune signalling may prove to be a novel target for future studies on pathogenic mechanisms and therapeutic approaches in retinal vasculitis. |
| Databáze: | OpenAIRE |
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