Histamine 4 receptor plays an important role in auto-antibody-induced arthritis
| Autor: | David Frommholz, Rolf Bräuer, Harald Illges, Mieczyslaw Gajda, Elisa Nent |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Immunology
Histamine Antagonists Arthritis Mice Transgenic Histamine H1 receptor Pharmacology Autoimmune Diseases Receptors G-Protein-Coupled Arthritis Rheumatoid Mice chemistry.chemical_compound Histamine receptor Mice Inbred NOD medicine Animals Immunology and Allergy Histamine H4 receptor Clozapine Autoantibodies Receptors Histamine H4 Thioperamide business.industry Glucose-6-Phosphate Isomerase Degranulation General Medicine Mast cell medicine.disease Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure chemistry Receptors Histamine business Histamine medicine.drug |
| Zdroj: | International Immunology. 25:437-443 |
| ISSN: | 1460-2377 0953-8178 |
| Popis: | Rheumatoid arthritis is a widespread autoimmune disease. In the murine K/B×N arthritis model, anti-GPI (anti-glucose 6-phosphate isomerase) antibodies lead to the formation of immune complexes. In the course of pathogenesis, these complexes activate the immune system and induce degranulation of mast cells, which are essential in this model of rheumatoid arthritis. A major mediator in mast cell granules is histamine, which is proven to be indispensable for joint inflammation in K/B×N mice. Histamine is known to bind to four different receptors (HR1–4), which have different expression profiles and exert a variety of different functions, including activation of the immune system. To analyze the contribution of the different histamine receptors, we employed histamine receptor antagonists (cetirizine, ranitidine, thioperamide and clozapine) blocking the receptors in C57BL/6 mice. Arthritis was induced via K/B×N serum injection. The results demonstrated that mice treated with all four histamine receptor antagonists simultaneously showed no arthritic symptoms, while positive control mice injected with K/B×N serum and vehicle suffered from severe symptoms. When antagonists specific for HR1–4 were applied individually, only the HR4 antagonist clozapine could protect mice from arthritis, reflecting its expression and functionality in the immune system. |
| Databáze: | OpenAIRE |
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