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Interferon-gamma-mediated pathways are induced in human CD34(+) haematopoietic stem cells.
Immunobiology. 2010 Jun; 215(6):452-7.I

Abstract

Pro-inflammatory cytokines like interferon-gamma (IFN-gamma) are considered to be important in the development of anaemia of chronic disease (ACD). Both, inhibitory and stimulatory activities of IFN-gamma on erythropoiesis have been observed in vitro earlier. IFN-gamma induces several biochemical pathways in human monocytes, among them neopterin formation by GTP-cyclohydrolase I (GTP-CH I) and tryptophan degradation by the enzyme indoleamine 2,3-dioxygenase (IDO). IDO-mediated tryptophan deprivation efficiently inhibits the growth of proliferating cells and microbes, thus we wanted to examine whether enhanced tryptophan degradation by monocytic precursor cells also suppresses erythropoiesis. Therefore, IFN-gamma-mediated pathways were investigated in human CD34(+) progenitor cells, and effects of IFN-gamma on the proliferative activity of different progenitor subpopulations were studied. Cells were either cultivated in agar-conditioned medium (ACM) or in medium containing erythroid growth factors interleukin-3 (IL-3) and stem cell factor (SCF; EGFCM). Stimulation of CD34(+) cells with IFN-gamma in different doses (either 5000U/ml once or 200 and 400U/ml every other day) induced tryptophan degradation and in parallel also neopterin formation. Unstimulated cells cultured with ACM produced higher amounts of neopterin and kynurenine (all p<0.05). IFN-gamma stimulated higher kynurenine and neopterin formation in cells cultivated in EGFCM, stimulation with 400U IFN-gamma every other day was most effective. IFN-gamma stimulated the growth and proliferation of CFU-E and BFU-E (3-8) in both media. In conclusion, stimulation of haematopoietic stem cells with IFN-gamma activates IDO and neopterin formation, and it also exerts an influence on the proliferation of various stem cell populations.

Authors+Show Affiliations

Clinical Immunology and Infectious Diseases, Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19765856

Citation

Kurz, Katharina, et al. "Interferon-gamma-mediated Pathways Are Induced in Human CD34(+) Haematopoietic Stem Cells." Immunobiology, vol. 215, no. 6, 2010, pp. 452-7.
Kurz K, Gluhcheva Y, Zvetkova E, et al. Interferon-gamma-mediated pathways are induced in human CD34(+) haematopoietic stem cells. Immunobiology. 2010;215(6):452-7.
Kurz, K., Gluhcheva, Y., Zvetkova, E., Konwalinka, G., & Fuchs, D. (2010). Interferon-gamma-mediated pathways are induced in human CD34(+) haematopoietic stem cells. Immunobiology, 215(6), 452-7. https://doi.org/10.1016/j.imbio.2009.08.007
Kurz K, et al. Interferon-gamma-mediated Pathways Are Induced in Human CD34(+) Haematopoietic Stem Cells. Immunobiology. 2010;215(6):452-7. PubMed PMID: 19765856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interferon-gamma-mediated pathways are induced in human CD34(+) haematopoietic stem cells. AU - Kurz,Katharina, AU - Gluhcheva,Yordanka, AU - Zvetkova,Elissaveta, AU - Konwalinka,Guenther, AU - Fuchs,Dietmar, Y1 - 2009/09/17/ PY - 2009/06/30/received PY - 2009/08/20/revised PY - 2009/08/22/accepted PY - 2009/9/22/entrez PY - 2009/9/22/pubmed PY - 2010/7/31/medline SP - 452 EP - 7 JF - Immunobiology JO - Immunobiology VL - 215 IS - 6 N2 - Pro-inflammatory cytokines like interferon-gamma (IFN-gamma) are considered to be important in the development of anaemia of chronic disease (ACD). Both, inhibitory and stimulatory activities of IFN-gamma on erythropoiesis have been observed in vitro earlier. IFN-gamma induces several biochemical pathways in human monocytes, among them neopterin formation by GTP-cyclohydrolase I (GTP-CH I) and tryptophan degradation by the enzyme indoleamine 2,3-dioxygenase (IDO). IDO-mediated tryptophan deprivation efficiently inhibits the growth of proliferating cells and microbes, thus we wanted to examine whether enhanced tryptophan degradation by monocytic precursor cells also suppresses erythropoiesis. Therefore, IFN-gamma-mediated pathways were investigated in human CD34(+) progenitor cells, and effects of IFN-gamma on the proliferative activity of different progenitor subpopulations were studied. Cells were either cultivated in agar-conditioned medium (ACM) or in medium containing erythroid growth factors interleukin-3 (IL-3) and stem cell factor (SCF; EGFCM). Stimulation of CD34(+) cells with IFN-gamma in different doses (either 5000U/ml once or 200 and 400U/ml every other day) induced tryptophan degradation and in parallel also neopterin formation. Unstimulated cells cultured with ACM produced higher amounts of neopterin and kynurenine (all p<0.05). IFN-gamma stimulated higher kynurenine and neopterin formation in cells cultivated in EGFCM, stimulation with 400U IFN-gamma every other day was most effective. IFN-gamma stimulated the growth and proliferation of CFU-E and BFU-E (3-8) in both media. In conclusion, stimulation of haematopoietic stem cells with IFN-gamma activates IDO and neopterin formation, and it also exerts an influence on the proliferation of various stem cell populations. SN - 1878-3279 UR - https://www.unboundmedicine.com/medline/citation/19765856/Interferon_gamma_mediated_pathways_are_induced_in_human_CD34_+__haematopoietic_stem_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0171-2985(09)00147-8 DB - PRIME DP - Unbound Medicine ER -