Wakabayashi Hiroyuki, Takakura Natsuko, Yamauchi Koji, Tamura Yoshitaka
Nutritional Science Laboratory, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa 228-8583, Japan.
Clin Vaccine Immunol. 2006 Feb;13(2):239-45. doi: 10.1128/CVI.13.2.239-245.2006.
Oral administration of lactoferrin (LF), an antimicrobial and immunomodulatory protein, shows a protective effect against infectious diseases, possibly via immunomodulation of the host. Initially, we confirmed an immunomodulatory effect of LF by observing changes in the number of cells in the leukocyte subsets in the peripheral blood and spleens of mice 1 day after oral administration of LF. Then we developed a quantitative reverse transcription-PCR method for 20 immunity-related genes of antimicrobial proteins, pattern recognition receptors, cytokines, and lymphocyte mobilization-related proteins, and we assessed the expression of these genes in the small intestines of mice 2 h after administration of water, bovine serum albumin (BSA), or LF. Expression of the LF gene was lower in mice administered LF than in mice administered water or BSA, implying a negative-feedback control. Expression of gamma interferon (IFN-gamma) and interleukin-10 (IL-10) was lower in both BSA- and LF-administered mice than in water administered mice, suggesting a nonspecific effect of protein ingestion. Expression of NOD2, IFN-beta, and IL-12p40 was higher with LF administration than with water or BSA administration. The expression levels of these three genes were correlated. This study indicated that oral administration of LF modulates the small intestinal expression of genes closely related to the host defense in a specific or a nonspecific manner.
乳铁蛋白(LF)是一种具有抗菌和免疫调节作用的蛋白质,口服LF对传染病具有保护作用,可能是通过对宿主的免疫调节来实现的。首先,我们通过观察口服LF一天后小鼠外周血和脾脏中白细胞亚群细胞数量的变化,证实了LF的免疫调节作用。然后,我们开发了一种针对20种与免疫相关基因的定量逆转录-聚合酶链反应方法,这些基因涉及抗菌蛋白、模式识别受体、细胞因子和淋巴细胞动员相关蛋白,并且我们评估了在给予水、牛血清白蛋白(BSA)或LF后2小时小鼠小肠中这些基因的表达。给予LF的小鼠中LF基因的表达低于给予水或BSA的小鼠,这意味着存在负反馈调控。给予BSA和LF的小鼠中γ干扰素(IFN-γ)和白细胞介素-10(IL-10)的表达均低于给予水的小鼠,这表明蛋白质摄入具有非特异性作用。给予LF后NOD2、IFN-β和IL-12p40的表达高于给予水或BSA后。这三个基因的表达水平具有相关性。本研究表明,口服LF以特异性或非特异性方式调节与宿主防御密切相关的小肠基因表达。