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Article Dans Une Revue PLoS ONE Année : 2010

Parathyroid Hormone Mediates Hematopoietic Cell Expansion through Interleukin-6

Flavia Q Pirih
  • Fonction : Auteur
Megan N Michalski
  • Fonction : Auteur
Sun W Cho
  • Fonction : Auteur
Amy J Koh
  • Fonction : Auteur
Janice E Berry
  • Fonction : Auteur
Eduardo Ghaname
  • Fonction : Auteur
Pachiyappan Kamarajan
  • Fonction : Auteur
Charles Ross
  • Fonction : Auteur
Yvonne Kapila
  • Fonction : Auteur
Laurie Mccauley
  • Fonction : Auteur

Résumé

Parathyroid hormone (PTH) stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6) is upregulated by PTH and stimulates hematopoiesis. The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L), PTH, Flt-3L plus PTH, or vehicle control. Flt-3L alone increased adherent and non-adherent cells. PTH did not directly impact hematopoietic or osteoclastic cells but acted in concert with Flt-3L to further increase cell numbers. Flt-3L alone stimulated proliferation, while PTH combined with Flt-3L decreased apoptosis. Flt-3L increased blasts early in culture, and later increased CD45 + and CD11b + cells. In parallel experiments, IL-6 acted additively with Flt-3L to increase cell numbers and IL-6-deficient bone marrow cultures (compared to wildtype controls) but failed to amplify in response to Flt-3L and PTH, suggesting that IL-6 mediated the PTH effect. In vivo, PTH increased Lin-Sca-1 + c-Kit + (LSK) hematopoietic progenitor cells after PTH treatment in wildtype mice, but failed to increase LSKs in IL-6-deficient mice. In conclusion, PTH acts with Flt-3L to maintain hematopoietic cells by limiting apoptosis. IL-6 is a critical mediator of bone marrow cell expansion and is responsible for PTH actions in hematopoietic cell expansion.
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Dates et versions

hal-02353427 , version 1 (07-11-2019)

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Flavia Q Pirih, Megan N Michalski, Sun W Cho, Amy J Koh, Janice E Berry, et al.. Parathyroid Hormone Mediates Hematopoietic Cell Expansion through Interleukin-6. PLoS ONE, 2010, 5 (10), pp.e13657. ⟨10.1371/journal.pone.0013657⟩. ⟨hal-02353427⟩
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