Induction of interleukin-12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1 response
Induction of interleukin-12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1 response
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DOI：
10.1046/j.1365-2567.2003.01673.x
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发表时间：
2003-07-01
期刊：
影响因子：
6.4
通讯作者：
Kim, SH
中科院分区：
文献类型：
--
作者：
Kim, TS;Kang, BY;Kim, SH
在这项研究中，我们调查是否小檗碱介导的诱导白细胞介素-12（IL-12）在抗原呈递细胞的生产可以调节抗原致敏的CD 4（+）T辅助（Th）细胞的细胞因子谱。小檗碱预处理诱导巨噬细胞和树突状细胞产生IL-12，并显着增加脂多糖刺激的巨噬细胞和CD 40配体刺激的树突状细胞产生IL-12的水平。重要的是，小檗碱预处理巨噬细胞增加了它们诱导干扰素-γ（IFN-γ）的能力，并降低了它们在抗原致敏的CD 4（+）T细胞中诱导IL-4的能力。小檗碱不影响巨噬细胞表面的II类主要组织相容性复合物分子，共刺激分子CD 80和CD 86，和细胞内粘附分子-1的表达。向小檗碱预处理的巨噬细胞和CD 4（+）T细胞培养物中加入中和性抗IL-12 p40单克隆抗体，恢复了抗原致敏的CD 4（+）T细胞中IL-4的产生。小檗碱的体内给药导致当在体外用脂多糖或热灭活的单核细胞增生李斯特菌刺激时，巨噬细胞产生IL-12的诱导增强，导致抗原致敏的CD 4（+）T细胞中Th 2型细胞因子谱的抑制（IL-4减少和IFN-γ产生增加）。这些发现可能指出小檗碱或含有小檗碱的药用植物在Th 2型细胞介导的免疫疾病如过敏性疾病中的可能治疗用途。
In this study we investigated whether berberine-mediated induction of interleukin-12 (IL-12) production in antigen-presenting cells could regulate a cytokine profile of antigen-primed CD4(+) T helper (Th) cells. Pretreatment with berberine induced IL-12 production in both macrophages and dendritic cells, and significantly increased the levels of IL-12 production in lipopylysaccharide-stimulated macrophages and in CD40 ligand-stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon-gamma (IFN-gamma) and reduced their ability to induce IL-4 in antigen-primed CD4(+) T cells. Berberine did not influence the macrophage cell surface expression of the class II major histocompatibility complex molecule, the co-stimulatory molecules CD80 and CD86, and intracellular adhesion molecule-1. Addition of neutralizing anti-IL-12p40 monoclonal antibody to cultures of berberine-pretreated macrophages and CD4(+) T cells restored IL-4 production in antigen-primed CD4(+) T cells. The In vivo administration of berberine resulted in the enhanced induction of IL-12 production by macrophages when stimulated in vitro with lipopolysaccharide or heat-killed Listeria monocytogenes, leading to the inhibition of the Th type 2 cytokine profile (decreased IL-4 and increased IFN-gamma production) in antigen-primed CD4(+) T cells. These findings may point to a possible therapeutic use of berberine or medicinal plants containing berberine in the Th type 2 cell-mediated immune diseases such as allergic diseases.