Human inflammatory dendritic epidermal cells express a functional histamine H4 receptor
Human inflammatory dendritic epidermal cells express a functional histamine H4 receptor
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DOI：
10.1038/sj.jid.5701250
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发表时间：
2008-07-01
影响因子：
6.5
通讯作者：
Gutzmer, Ralf
中科院分区：
文献类型：
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作者：
Dijkstra, Dorothea;Stark, Holger;Gutzmer, Ralf
白细胞上组胺H-4受体(H4R)的表达提示该受体具有免疫调节作用。在这里，我们研究了H4R在人炎症树突状表皮细胞(IDECs)上的表达和功能。H4R通过皮肤的IDEC表达。在单核细胞来源的IDECs(Mo-IDECs)上，H4R也被表达，并被干扰素-γ上调。在功能上，组胺和H4R激动剂氯苯普妥和4-甲基组胺下调Mo-IDEC上Th2连接的趋化因子CCL2和Th1细胞因子IL-12的产生，而其他组胺受体激动剂不能。H4R选择性拮抗剂(JNJ7777120)可阻断H4R激动剂的作用。CCL2的下调也导致单核细胞迁移减少。因此，IDEC表达一种功能活跃的H4R，在刺激下导致CCL2和IL-12的下调。这可能对特应性皮炎的治疗有意义，因为H4R激动剂可能在抑制炎症方面有有益的效果。
Expression of histamine H-4 receptor (H4R) on leukocytes suggests an immunomodulatory role of this receptor. Here we investigated the expression and function of H4R on human inflammatory dendritic epidermal cells (IDECs). H4R is expressed by IDEC of the skin. On monocyte-derived IDECs (Mo-IDECs), H4R is also expressed and upregulated by IFN-gamma. Functionally, histamine and H4R agonists clobenpropit and 4-methylhistamine downregulated the production of the Th2-linked chemokine CCL2 and the Th1 cytokine IL-12 on Mo-IDEC, whereas agonists for the other histamine receptors did not. An H4R-selective antagonist (JNJ7777120) blocked the effect of H4R agonists. Downregulation of CCL2 also led to a decreased migration of monocytes. Thus, IDEC express a functionally active H4R, which upon stimulation leads to downregulation of CCL2 and IL-12. This might have implications for the treatment of atopic dermatitis, since H4R agonists may have beneficial effects in downregulating inflammation.