title: Histamine 4 receptor plays an important role in auto-antibody-induced arthritis.
abstract: 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.
authors.affiliation: University of Applied Sciences, Department of Natural Sciences, Immunology and Cell Biology, von-Liebig-Str. 20, D-53359 Rheinbach, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nent
authors.forename: David
authors.initials: D
authors.lastname: Frommholz
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Harald
authors.initials: H
authors.lastname: Illges
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D003024:Clozapine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology; D006633:Histamine Antagonists / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011968:Receptors, Histamine / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000074040:Receptors, Histamine H4
chemical_list: D001323:Autoantibodies; D006633:Histamine Antagonists; C498829:Hrh4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D005956:Glucose-6-Phosphate Isomerase; D003024:Clozapine
keywords: K/B×N model; autoimmune disease; histamine receptor antagonist