Objective. We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies to demonstrate that stimulation of gamma-globin gene expression is also mediated by NOS induction in stromal cells within the bone marrow microenvironment. Materials and Methods. Using NO analyzer, we measured NO production in endothelial and macrophage cell cultures. In coculture studies of erythroid and stromal cells, we measured globin gene expression during stimulation by NO induers. Results. Hydroxyurea (30 - 100 mu M) induced NOS-dependent production of NO in human macrophages (up to 1.2 mu M). Coculture studies of human macrophages with erythroid progenitor cells also resulted in induction of gamma-globin mRNA expression (up to threefold) in the presence of hydroxy...urea. NOS-dependent stimulation of NO by lipopolysaccharide (up to 0.6 mu M) has been observed in human macrophages. We found that lipopolysaccharide and interferon-gamma together increased gamma-globin gene expression (up to twofold) in human macrophage/erythroid cell cocultures. Coculture of human bone marrow endothelial cells with erythroid progenitor cells also induced gamma-globin mRNA expression (2.4-fold) in the presence of hydroxyurea (40 mu M). Conclusion. These results demonstrate an arrangement by which NO and fetal hemoglobin inducers may stimulate globin genes in erythroid cells via the common paracrine effect of bone marrow stromal cells.
Source:
Experimental Hematology, 2009, 37, 10, 1230-1237
Publisher:
Elsevier Science Inc, New York
Funding / projects:
Intramural Research Program of the National Institutes of Health (Bethesda, MD, USA)
Intramural Research Program at the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, USA
TY - JOUR
AU - Čokić, Vladan
AU - Beleslin-Čokić, Bojana
AU - Smith, Reginald D.
AU - Economou, Antaeus P.
AU - Wahl, Larry M.
AU - Noguchi, Constance T.
AU - Schechter, Alan N.
PY - 2009
UR - http://rimi.imi.bg.ac.rs/handle/123456789/223
AB - Objective. We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies to demonstrate that stimulation of gamma-globin gene expression is also mediated by NOS induction in stromal cells within the bone marrow microenvironment. Materials and Methods. Using NO analyzer, we measured NO production in endothelial and macrophage cell cultures. In coculture studies of erythroid and stromal cells, we measured globin gene expression during stimulation by NO induers. Results. Hydroxyurea (30 - 100 mu M) induced NOS-dependent production of NO in human macrophages (up to 1.2 mu M). Coculture studies of human macrophages with erythroid progenitor cells also resulted in induction of gamma-globin mRNA expression (up to threefold) in the presence of hydroxyurea. NOS-dependent stimulation of NO by lipopolysaccharide (up to 0.6 mu M) has been observed in human macrophages. We found that lipopolysaccharide and interferon-gamma together increased gamma-globin gene expression (up to twofold) in human macrophage/erythroid cell cocultures. Coculture of human bone marrow endothelial cells with erythroid progenitor cells also induced gamma-globin mRNA expression (2.4-fold) in the presence of hydroxyurea (40 mu M). Conclusion. These results demonstrate an arrangement by which NO and fetal hemoglobin inducers may stimulate globin genes in erythroid cells via the common paracrine effect of bone marrow stromal cells.
PB - Elsevier Science Inc, New York
T2 - Experimental Hematology
T1 - Stimulated stromal cells induce gamma-globin gene expression in erythroid cells via nitric oxide production
EP - 1237
IS - 10
SP - 1230
VL - 37
DO - 10.1016/j.exphem.2009.06.009
ER -
@article{
author = "Čokić, Vladan and Beleslin-Čokić, Bojana and Smith, Reginald D. and Economou, Antaeus P. and Wahl, Larry M. and Noguchi, Constance T. and Schechter, Alan N.",
year = "2009",
abstract = "Objective. We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies to demonstrate that stimulation of gamma-globin gene expression is also mediated by NOS induction in stromal cells within the bone marrow microenvironment. Materials and Methods. Using NO analyzer, we measured NO production in endothelial and macrophage cell cultures. In coculture studies of erythroid and stromal cells, we measured globin gene expression during stimulation by NO induers. Results. Hydroxyurea (30 - 100 mu M) induced NOS-dependent production of NO in human macrophages (up to 1.2 mu M). Coculture studies of human macrophages with erythroid progenitor cells also resulted in induction of gamma-globin mRNA expression (up to threefold) in the presence of hydroxyurea. NOS-dependent stimulation of NO by lipopolysaccharide (up to 0.6 mu M) has been observed in human macrophages. We found that lipopolysaccharide and interferon-gamma together increased gamma-globin gene expression (up to twofold) in human macrophage/erythroid cell cocultures. Coculture of human bone marrow endothelial cells with erythroid progenitor cells also induced gamma-globin mRNA expression (2.4-fold) in the presence of hydroxyurea (40 mu M). Conclusion. These results demonstrate an arrangement by which NO and fetal hemoglobin inducers may stimulate globin genes in erythroid cells via the common paracrine effect of bone marrow stromal cells.",
publisher = "Elsevier Science Inc, New York",
journal = "Experimental Hematology",
title = "Stimulated stromal cells induce gamma-globin gene expression in erythroid cells via nitric oxide production",
pages = "1237-1230",
number = "10",
volume = "37",
doi = "10.1016/j.exphem.2009.06.009"
}
Čokić, V., Beleslin-Čokić, B., Smith, R. D., Economou, A. P., Wahl, L. M., Noguchi, C. T.,& Schechter, A. N.. (2009). Stimulated stromal cells induce gamma-globin gene expression in erythroid cells via nitric oxide production. in Experimental Hematology
Elsevier Science Inc, New York., 37(10), 1230-1237.
https://doi.org/10.1016/j.exphem.2009.06.009
Čokić V, Beleslin-Čokić B, Smith RD, Economou AP, Wahl LM, Noguchi CT, Schechter AN. Stimulated stromal cells induce gamma-globin gene expression in erythroid cells via nitric oxide production. in Experimental Hematology. 2009;37(10):1230-1237.
doi:10.1016/j.exphem.2009.06.009 .
Čokić, Vladan, Beleslin-Čokić, Bojana, Smith, Reginald D., Economou, Antaeus P., Wahl, Larry M., Noguchi, Constance T., Schechter, Alan N., "Stimulated stromal cells induce gamma-globin gene expression in erythroid cells via nitric oxide production" in Experimental Hematology, 37, no. 10 (2009):1230-1237,
https://doi.org/10.1016/j.exphem.2009.06.009 . .
