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自身免疫性疾病中的组胺H4受体。

The histamine H4 receptor in autoimmune disease.

作者信息

Zhang Mai, Venable Jennifer D, Thurmond Robin L

机构信息

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.

出版信息

Expert Opin Investig Drugs. 2006 Nov;15(11):1443-52. doi: 10.1517/13543784.15.11.1443.

Abstract

Histamine exerts its actions through four known receptors. The recently cloned histamine receptor, H4R, has been shown to have a role in chemotaxis and mediator release in various types of immune cells including mast cells, eosinophils, dendritic cells and T cells. H4R antagonists have been shown to have anti-inflammatory properties and efficacy in a number of disease models, such as those for asthma and colitis in vivo. Recently, H4R antagonists have been developed with high receptor affinity and specificity, which make them good tools for further characterisation of the receptor in animal models and, eventually, in humans. Histamine and the cells that produce it, such as mast cells and basophils, have long been thought to be involved in allergic conditions but there has recently been recognition that they may also play a role in various autoimmune diseases. Given this and the fact that the H4R has function in mast cells, dendritic cells and T cells, antagonists for the receptor may be useful in treating autoimmune diseases in addition to allergy.

摘要

组胺通过四种已知受体发挥作用。最近克隆出的组胺受体H4R,已被证明在包括肥大细胞、嗜酸性粒细胞、树突状细胞和T细胞在内的多种免疫细胞的趋化性和介质释放中发挥作用。H4R拮抗剂在多种疾病模型中已显示出抗炎特性和疗效,如体内哮喘和结肠炎模型。最近,已开发出具有高受体亲和力和特异性的H4R拮抗剂,这使其成为在动物模型以及最终在人体中进一步表征该受体的良好工具。长期以来,组胺及其产生细胞,如肥大细胞和嗜碱性粒细胞,一直被认为与过敏性疾病有关,但最近人们认识到它们也可能在各种自身免疫性疾病中起作用。鉴于此,以及H4R在肥大细胞、树突状细胞和T细胞中具有功能这一事实,该受体的拮抗剂除了可用于治疗过敏外,可能对治疗自身免疫性疾病也有用。

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