2005 Fiscal Year Final Research Report Summary
Breast milk-derived factors (especially, lactoferrin and TGF-β) and milk-borne retroviruses
| Project/Area Number |
16591041
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Nagasaki University |
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Principal Investigator |
MORIUCHI Masako Nagasaki University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (60322301)
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| Co-Investigator(Kenkyū-buntansha) |
MORIUCHI Hiroyuki Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (90315234)
SATO Hiroshi Nagasaki University, Center for Frontier Life Sciences, Professor, 先導生命科学研究支援センター, 教授 (50072947)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Lactoferrin / HIV / HTLV-I / Rotavirus / Promoter / Tax / Mammary epithelial cells / TGF-β |
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| Research Abstract |
Effect of TGF-β on HIV-1 Infection
TGF-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 Lactoferrin
Lactoferrin 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 Expression
Lactoferrin 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.
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