Histamine regulation of interleukin-18-initiating cytokine cascade is associated with down-regulation of intercellular adhesion molecule-1 expression in human peripheral blood mononuclear cells.
Histamine regulation of interleukin-18-initiating cytokine cascade is associated with down-regulation of intercellular adhesion molecule-1 expression in human peripheral blood mononuclear cells.
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DOI：
10.1124/jpet.300.1.227
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Hideo Takahashi;A. Yoshida;H. Iwagaki;T. Yoshino;H. Itoh;T. Morichika;M. Yokoyama;T. Akagi;N. Tanaka;S. Mori;M. Nishibori
中科院分区：
文献类型：
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作者：
Hideo Takahashi;A. Yoshida;H. Iwagaki;T. Yoshino;H. Itoh;T. Morichika;M. Yokoyama;T. Akagi;N. Tanaka;S. Mori;M. Nishibori
在先前的研究中，我们证明了白细胞介素（IL）-18上调人外周血单核细胞（PBMC）中单核细胞上的细胞间粘附分子-1（ICAM-1）的表达，并且单核细胞/T细胞或NK细胞之间通过ICAM-1/LFA-1的异型相互作用增强了PBMC中IL-12、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）的产生。在本研究中，我们证明，组胺抑制ICAM-1的表达在单核细胞诱导的IL-18使用流式细胞仪和IL-12，IFN-γ，TNF-α诱导的IL-18的反应是浓度依赖性抑制共存的组胺，而IL-18抑制IL-10的生产被逆转相同浓度的组胺。组胺对ICAM-1表达和细胞因子产生的调节作用均被法莫替丁浓度依赖性地拮抗，但不被d-氯苯那敏和硫代哌丁胺拮抗，并被选择性H（2）受体激动剂模拟，但不被H（1）和H（3）受体激动剂模拟，表明H（2）受体参与组胺作用。组胺对IL-18诱导的IFN-γ的抑制归因于组胺对IL-12产生的强烈抑制。因此，组胺通过对单核细胞中ICAM-1表达和IL-12产生的强烈抑制作用，对IL-18激活的细胞因子级联反应发挥负反馈机制，有助于形成从Th 1到Th 2的多种细胞因子激活模式，这取决于单核细胞/巨噬细胞激活和细胞因子环境。
In the previous study, we demonstrated that interleukin (IL)-18 up-regulated intercellular adhesion molecule-1 (ICAM-1) expression on monocytes in human peripheral blood mononuclear cells (PBMC) and that heterotypic interaction between monocytes/T or NK cells through ICAM-1/LFA-1 intensified the production of IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) in PBMC. In the present study, we demonstrate that histamine inhibited the ICAM-1 expression in monocytes induced by IL-18 using flow cytometry and that the responses of IL-12, IFN-gamma, and TNF-alpha induced by IL-18 were concentration dependently inhibited by coexisting histamine, whereas IL-18-inhibited IL-10 production was reversed by the same concentrations of histamine. The modulatory effects of histamine on ICAM-1 expression and cytokine production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H(2)-receptor agonists but not by H(1)- and H(3)-receptor agonists, indicating the involvement of H(2)-receptors in histamine action. The inhibition of IL-18-induced IFN-gamma by histamine was ascribed to the strong inhibition of IL-12 production by histamine. Histamine thus operates the negative feedback mechanism against IL-18-activated cytokine cascade through the strong inhibitory effect on ICAM-1 expression and IL-12 production in monocytes, contributing to the formation of diverse pattern of cytokine activation from Th1 to Th2, depending on the monocyte/macrophage activation and cytokine environment.