Lactoferrin (Lf) is an iron-binding glycoprotein, and involved in immunomodulation. However, the molecular mechanism underlying the biological functions of Lf on immune systems remains poorly understood. Recent studies on Lf have been reported its inhibitory influence on growth of tumor cells. The p...
Lactoferrin (Lf) is an iron-binding glycoprotein, and involved in immunomodulation. However, the molecular mechanism underlying the biological functions of Lf on immune systems remains poorly understood. Recent studies on Lf have been reported its inhibitory influence on growth of tumor cells. The present study purposes to investigate anti-tumor effects bovine Lf (B-Lf) using C57BL/6J mouse, which were abdominally injected with B16 melanoma tumor cells. A relatively high dose of B-Lf, 1 g/kg/day, in diet inhibited efficiently the tumor growth. In order to elucidate the reaction mechanism of B-Lf on the tumor growth, a variety of cytokines involved in cell growth control and immunity were analyzed in tissue culture systems. Levels of keratinocyte chemoattractant (KC) and Macrophage inflammatory protein-2 (MIP-2) as murine cytokines were monitored. As a result, Lf enhanced the promoter strength of KC, MIP-2, and Cox-2, but decreased significantly their LPS-stimulated promoter activities. In order to identify the responsive elements to Lf, the binding sites for major transcription factors, NF-kB and AP-1, on the promoter region of the KC were analyzed. Analysis with series deletion mutants revealed that a binding consensus of AP-1, rather than NF-kB, was found to be critical in response to Lf. As human IL-8 is known to act similarly as KC, sensitivity of IL-8 gene promoter to Lf in human cell was investigated in a similar way. RT-PCR analysis showed that the mRNA level of IL-8 was indeed increased in cells incubated with Lf. The promoter of IL-8 gene also contains binding sites of both NF-kB and AP-1, however, the mutational analysis indicated that binding consensuses of both major transcription factors are required. In addition, this study showed that Lf activated the production nitric oxide, NO. Consequently, Lf was found to be a potential agonist in a variety of immunological defense system.
Lactoferrin (Lf) is an iron-binding glycoprotein, and involved in immunomodulation. However, the molecular mechanism underlying the biological functions of Lf on immune systems remains poorly understood. Recent studies on Lf have been reported its inhibitory influence on growth of tumor cells. The present study purposes to investigate anti-tumor effects bovine Lf (B-Lf) using C57BL/6J mouse, which were abdominally injected with B16 melanoma tumor cells. A relatively high dose of B-Lf, 1 g/kg/day, in diet inhibited efficiently the tumor growth. In order to elucidate the reaction mechanism of B-Lf on the tumor growth, a variety of cytokines involved in cell growth control and immunity were analyzed in tissue culture systems. Levels of keratinocyte chemoattractant (KC) and Macrophage inflammatory protein-2 (MIP-2) as murine cytokines were monitored. As a result, Lf enhanced the promoter strength of KC, MIP-2, and Cox-2, but decreased significantly their LPS-stimulated promoter activities. In order to identify the responsive elements to Lf, the binding sites for major transcription factors, NF-kB and AP-1, on the promoter region of the KC were analyzed. Analysis with series deletion mutants revealed that a binding consensus of AP-1, rather than NF-kB, was found to be critical in response to Lf. As human IL-8 is known to act similarly as KC, sensitivity of IL-8 gene promoter to Lf in human cell was investigated in a similar way. RT-PCR analysis showed that the mRNA level of IL-8 was indeed increased in cells incubated with Lf. The promoter of IL-8 gene also contains binding sites of both NF-kB and AP-1, however, the mutational analysis indicated that binding consensuses of both major transcription factors are required. In addition, this study showed that Lf activated the production nitric oxide, NO. Consequently, Lf was found to be a potential agonist in a variety of immunological defense system.
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