Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis

被引:43
作者
Rossbach, K. [1 ]
Schaper, K. [2 ]
Kloth, Ch. [3 ]
Gutzmer, R. [2 ]
Werfel, T. [2 ]
Kietzmann, M. [1 ]
Baeumer, W. [1 ,4 ]
机构
[1] Univ Vet Med, Inst Pharmacol Toxicol & Pharm, Bunteweg 17, D-30559 Hannover, Germany
[2] Hannover Med Sch, Dept Dermatol & Allergy, Div Immunodermatol & Allergy Res, Hannover, Germany
[3] Hannover Med Sch, Inst Pharmacol, Hannover, Germany
[4] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA
关键词
Allergic inflammation; atopic dermatitis; histamine H4 receptor; OVA; H-4; RECEPTOR; AIRWAY INFLAMMATION; ALLERGIC DERMATITIS; ANTAGONISM; SKIN; TARGET; POTENT; ADULTS; CELLS;
D O I
10.1111/all.12779
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
BackgroundThe 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. Material and methodsThe development of ovalbumin-induced AD-like skin lesions was analysed in H4R(-/-) mice and in H4R antagonist (JNJ28307474)-treated mice. ResultsH4R(-/-) 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. ConclusionThe 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.
引用
收藏
页码:189 / 197
页数:9
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