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盐酸依匹斯汀对人外周血CD4 + T细胞体外产生胸腺和活化调节趋化因子的抑制活性。

Suppressive activity of epinastine hydrochloride on TARC production from human peripheral blood CD4+ T cells in-vitro.

作者信息

Kanai Ken-Ichi, Asano Kazuhito, Hisamitsu Tadashi, Suzaki Harumi

机构信息

Department of Otolaryngology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

出版信息

J Pharm Pharmacol. 2005 Aug;57(8):1027-36. doi: 10.1211/0022357056640.

Abstract

Thymus- and activation-regulated chemokine (TARC) is an important molecule in the development and maintenance of allergic diseases. However, there is little information about the influence of anti-allergic agents on TARC production. The aim of this study is to examine the influence of epinastine hydrochloride, an H1-receptor antagonist, on TARC production from human peripheral blood CD4+ T cells using an in-vitro cell culture technique. CD4+ T cells prepared from healthy subjects were cultured in wells coated with a combination of OKT3 and anti-CD28 monoclonal antibody in the presence or absence of epinastine HCl for 24 h. The cells were also stimulated with interleukin (IL)-4 in a similar manner. Levels of TARC and IL-4 in culture supernatants were examined by ELISA. The addition of epinastine HCl exerted a dose-dependent suppressive effect on the production of both TARC and IL-4 from CD4+ T cells under co-stimulatory molecule stimulation. The minimum concentration of the agent showing a significant suppressive effect on TARC and IL-4 production was 5.0 microM and 2.5 microM, respectively. Epinastine HCl also suppressed the ability of cells to produce TARC in response to IL-4 stimulation, when the agent was added to cell cultures at more than 2.5 microM. It was concluded that this inhibitory action of epinastine HCl may be partially responsible for epinastine's attenuating effect on allergic diseases.

摘要

胸腺与活化调节趋化因子(TARC)是变应性疾病发生发展及维持过程中的一种重要分子。然而,关于抗变应原药物对TARC产生的影响,目前所知甚少。本研究旨在采用体外细胞培养技术,研究H1受体拮抗剂盐酸依匹斯汀对人外周血CD4+T细胞产生TARC的影响。将健康受试者制备的CD4+T细胞在包被有OKT3和抗CD28单克隆抗体的孔中培养,同时加入或不加入盐酸依匹斯汀,培养24小时。细胞也以类似方式用白细胞介素(IL)-4刺激。通过酶联免疫吸附测定法检测培养上清液中TARC和IL-4的水平。在共刺激分子刺激下,加入盐酸依匹斯汀对CD4+T细胞产生TARC和IL-4均有剂量依赖性抑制作用。对TARC和IL-4产生显示出显著抑制作用的该药物的最低浓度分别为5.0微摩尔/升和2.5微摩尔/升。当以大于2.5微摩尔/升的浓度将盐酸依匹斯汀加入细胞培养物中时,它也抑制细胞对IL-4刺激产生TARC的能力。得出的结论是,盐酸依匹斯汀的这种抑制作用可能部分解释了依匹斯汀对变应性疾病的减轻作用。

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