title: Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis.
abstract: BACKGROUND
  The histamine H4 receptor (H4R) was brought into focus as a new therapeutic target for the treatment of allergic disorders such as atopic dermatitis (AD). H4R antagonists have already been tested in several animal models of AD, but these studies have yielded conflicting results.
  
  
  METHODS
  The development of ovalbumin-induced AD-like skin lesions was analysed in H4R(-/-) mice and in H4R antagonist (JNJ28307474)-treated mice.
  
  
  RESULTS
  H4R(-/-) mice showed a clear amelioration of the skin lesions, with a diminished influx of inflammatory cells and a reduced epidermal hyperproliferation at lesional skin sites. H4R(-/-) mice had a reduced amount of ovalbumin-specific IgE, a reduced number of splenocytes and lymph node cells with a decreased number of CD4+ T cells. The H4R modulated the cytokine secretion of CD4+ T cells and splenocytes and altered the cellular profile in the lymph nodes. The anti-inflammatory effect could only partially be mimicked by JNJ28307474 and only when the H4R antagonist was given during sensitization and challenge and not when JNJ28307474 was only given during the provocation phase of the allergic reaction.
  
  
  CONCLUSIONS
  The H4R modulates inflammation in a chronic allergic dermatitis setting. However, results of this study indicate that it is necessary to block the H4R during ontogeny and development of the allergic inflammation.
authors.affiliation: Institute for Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Rossbach
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schaper
authors.affiliation: Institute for Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Ch
authors.initials: Ch
authors.lastname: Kloth
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Werfel
authors.affiliation: Institute for Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kietzmann
authors.affiliation: Institute for Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.|Department of Molecular Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, USA.
authors.forename: W
authors.initials: W
authors.lastname: Bäumer
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000009:adverse effects; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D011968:Receptors, Histamine / Q000172:deficiency* / Q000235:genetics; D000074040:Receptors, Histamine H4; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; C498829:Hrh4 protein, mouse; C000594390:JNJ28307474; D010880:Piperidines; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Allergic inflammation; OVA; atopic dermatitis; histamine H4 receptor