title: Interleukin-6 (IL-6) and low O(2) concentration (1%) synergize to improve the maintenance of hematopoietic stem cells (pre-CFC).
abstract: Low O(2) concentration (1%) favors the self-renewal of hematopoietic stem cells and inhibits committed progenitors (CFC). Since IL-6 influences both stem cells and committed progenitors at 20% O(2), we studied its effects in cultures at 1% O(2). The pre-CFC activity in Lin- population of mouse bone marrow was analyzed following 10 days of serum-free culture in medium (LC1) supplemented with IL-3 with and without IL-6, at 20 and 1% O(2) and phenotypic differentiation and proliferative history monitored. The IL-6 receptor expression and initiation of VEGF-A synthesis were also investigated. At 20% O(2), the effects of IL-6 on pre-CFC were negligible but effects on CFC were apparent; conversely, at 1% O(2), the IL-6 enhances activity of pre-CFC but not of CFC. Unlike at 20% O(2), at 1% O(2) a subpopulation of cells remained Lin- in spite of extensive proliferation. However, the absolute number of Lin- cells, did not correlate with pre-CFC activity. A relative increase in VEGF transcripts at 1% O(2) in presence of IL-3 alone was enhanced by the addition of IL-6. IL-6 enhanced pre-CFC activity at 1% O(2) and this was correlated to the induction of VEGF. These data reinforce the concept that physiologically low oxygenation of bone marrow is a regulator of stem cell maintenance. Since the 20% O(2) does not exist in tissues in vivo, further studies in vitro at lower O(2) concentrations should revise our knowledge relating to cytokine effects on stem and progenitor cells.
authors.affiliation: Faculty of Veterinary Medicine, University of Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Kovacević-Filipović
authors.forename: Marijana
authors.initials: M
authors.lastname: Petakov
authors.forename: Francis
authors.initials: F
authors.lastname: Hermitte
authors.forename: Christelle
authors.initials: C
authors.lastname: Debeissat
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Krstić
authors.forename: Gordana
authors.initials: G
authors.lastname: Jovcić
authors.forename: Dijana
authors.initials: D
authors.lastname: Bugarski
authors.forename: Xavier
authors.initials: X
authors.lastname: Lafarge
authors.forename: Pavle
authors.initials: P
authors.lastname: Milenković
authors.forename: Vincent
authors.initials: V
authors.lastname: Praloran
authors.forename: Zoran
authors.initials: Z
authors.lastname: Ivanović
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D053698:Interleukin-6 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D010100:Oxygen / Q000494:pharmacology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D053650:Interleukin-3 Receptor alpha Subunit; D015850:Interleukin-6; D053698:Interleukin-6 Receptor alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen