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Breast milk-derived factors (especially, lactoferrin and TGF-β) and milk-borne retroviruses

母乳衍生因子（尤其是乳铁蛋白和 TGF-β）和乳源性逆转录病毒

基本信息

批准号：
16591041
负责人：
MORIUCHI Masako
金额：
$ 2.37万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591041/
关键词：
Lactoferrin HIV HTLV-I Rotavirus Promoter Tax Mammary epithelial cells TGF-β HTLV-1 HIV-1 マクロファージ

项目摘要

Effect of TGF-β on HIV-1 InfectionTGF-β mediated differential effect on HIV-1 infection, depending on cell types. Among 3 cell types found in breast milk, TGF-β suppressed HIV-1 infection of mammary epithelial MCF-7 cells, enhanced that of macrophages, and had little effect on that of lymphocytes. TGF-β signaled NF-kB pathway, resulting in transcriptional repression of LTR promoter in MCF-7 cells and activation in macrophages. In MCF-7 cells, TGF-β induction of I-kB kinase played a critical role.In Vivo Antiviral Effect of LactoferrinLactoferrin has been shown to inhibit in vitro infection with a number of viruses ; however, its efficacy has rarely been confirmed in vivo. Therefore, we investigated whether orally administered lactoferrin could prevent or ameliorate rotaviral gastroenteritis in nurseries and kindergartens. We have demonstrated that lactoferrin had little effect on incidence of rotaviral gastroenteritis, but significantly reduced severity of disease.HTLV-I Tax Induction of Lactoferrin ExpressionLactoferrin in breast mile is derived from mammary epithelium and neutrophils. We have demonstrated that lactoferrin gene expression was induced by co-culture of mammary epithelial MCF-7 cells or neutrophil-differentiated HL-60 cells with HTLV-I-infected MT-2 cells. Such effect could be replaced with cell-free MT-2 culture supernatants or recombinant HTLV-I Tax protein. We have also demonstrated that Tax could transactivate lactoferrin promoter. Taken together with our previous study demonstrating that lactoferrin can transactivate HTLV-I LTR promoter, mutual interaction between lactoferrin and HTLV-I Tax may play an important role in milk-borne transmission of this virus.

TGF-β 对 HIV-1 感染的影响 TGF-β 对 HIV-1 感染的介导作用不同，具体取决于细胞类型。在母乳中发现的 3 种细胞类型中，TGF-β 抑制乳腺上皮 MCF-7 细胞的 HIV-1 感染，增强巨噬细胞的感染，而对淋巴细胞的影响很小。 TGF-β 向 NF-kB 通路发出信号，导致 MCF-7 细胞中 LTR 启动子的转录抑制和巨噬细胞中的激活。在 MCF-7 细胞中，TGF-β 诱导的 I-kB 激酶发挥了关键作用。乳铁蛋白的体内抗病毒作用乳铁蛋白已被证明可以抑制多种病毒的体外感染；然而，其功效很少在体内得到证实。因此，我们研究了托儿所和幼儿园口服乳铁蛋白是否可以预防或改善轮状病毒性胃肠炎。我们已经证明乳铁蛋白对轮状病毒性胃肠炎的发病率影响不大，但显着降低了疾病的严重程度。乳铁蛋白表达的HTLV-I税收诱导乳铁蛋白来源于乳腺上皮和中性粒细胞。我们已经证明乳铁蛋白基因表达是通过乳腺上皮MCF-7细胞或中性粒细胞分化的HL-60细胞与HTLV-I感染的MT-2细胞的共培养来诱导的。这种效果可以用无细胞MT-2培养上清液或重组HTLV-I Tax蛋白来替代。我们还证明了 Tax 可以反式激活乳铁蛋白启动子。结合我们之前的研究表明，乳铁蛋白可以反式激活HTLV-I LTR启动子，乳铁蛋白和HTLV-I Tax之间的相互作用可能在该病毒的乳源性传播中发挥重要作用。