Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis
Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis
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DOI：
10.1111/all.12779
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发表时间：
2016-02-01
期刊：
影响因子：
12.4
通讯作者：
Baeumer, W.
中科院分区：
文献类型：
--
作者：
Rossbach, K.;Schaper, K.;Baeumer, W.
背景组胺H4受体（histamine H4 receptor，H4 R）作为治疗特应性皮炎（atopic dermatitis，AD）等变态反应性疾病的新靶点而受到关注。H4 R拮抗剂已经在AD的几种动物模型中进行了测试，但是这些研究产生了相互矛盾的结果。材料和方法在H4 R（-/-）小鼠和H4 R拮抗剂中分析了卵清蛋白诱导的AD样皮肤病变的发展。结果H4 R（-/-）小鼠的皮肤损伤明显改善，减少了炎性细胞的流入和减少了损伤皮肤部位的表皮过度增殖。H4 R（-/-）小鼠卵清蛋白特异性IgE的量减少，脾细胞和淋巴结细胞数量减少，CD 4 + T细胞数量减少。H4 R调节CD 4 + T细胞和脾细胞的细胞因子分泌，并改变淋巴结中的细胞分布。抗炎作用只能部分模仿JNJ 28307474，只有当H4 R拮抗剂在致敏和挑战，而不是当JNJ 28307474只在激发阶段的过敏reaction.ConclusionThe H4 R调制炎症在慢性过敏性皮炎设置。然而，本研究的结果表明，在过敏性炎症的个体发生和发展过程中，阻断H4 R是必要的。
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.