Effects of naturin 2 on colony formation by hematopoietic progenitor cells in human umbilical cord blood mediated by induction of release of growth factors.
Naturin 2, a health drink, contains a mixture of Chinese herb plants and is a potent immunomodulator. It has anti-tumor effects mediated by immune system. In the present study, low density (LD) and purified CD34+ cells (enriched for hematopoietic stem [HSC] and progenitor [HPC]) from human umbilical cord blood (CB) were assayed for colony formation in response to Naturin 2. First, we examined the in vitro activity of Naturin 2 on HPC. Naturin 2 by itself stimulated colony formation derived from either LD or CD34+ CB cells. The stimulatory effect by Naturin 2 was mediated by both direct and indirect action on HSCs/HPCs. The indirect action is via releasing of cytokines in the 5 day-conditioned media by LD CB cells with Naturin 2. The stimulatory activities in the 5 day-conditioned media (CM) could be blocked by the neutralization antibodies against interleukin (IL)-3, granulocyte macrophage (GM)-colony stimulating factor (CSF), IL-1 alpha, IL-1 beta and M-CSF. Therefore, the stimulatory activities detected in the media conditioned are due to the cytokines released in the cultures. In addition, we have also determined that addition of Naturin 2 to the cultures with LD or CD34+ cells stimulated by IL-3 and/or GM-CSF resulted in a decrease of colony formation. The inhibitory effect of Naturin 2 was mediated, at least in part, by releasing suppressive cytokines, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, in the 3 day--CM, since antibodies against these two suppressive cytokines partially blocked the inhibitory activity. These results demonstrate that Naturin 2 has differential effects on hematopoiesis.
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Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202-5254, USA. llu@iupui.edu
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D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned; D004365:Drugs, Chinese Herbal / Q000378:metabolism* / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism* / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D017077:Culture Media, Conditioned; D004365:Drugs, Chinese Herbal; D006133:Growth Substances; D007155:Immunologic Factors; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha; C109348:naturin 2; D004921:Erythropoietin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor