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Spontaneous and inducible production of leukaemia inhibitory factor by human bone marrow stromal cells

V Lorgeot1, F Rougier, P Fixe

  • 1Laboratoire d'Hématologie Expérimentale,, Faculté de Médecine, 2 rue Dr. Marcland, Limoges, 87025, France.

Cytokine
|November 5, 1997
PubMed

Insights

Human bone marrow stromal cells produce leukaemia inhibitory factor (LIF). Cytokines like IL-1 and TNF-alpha stimulate LIF production, suggesting stromal cells are a key source of this growth factor in bone marrow.

Area of Science:

  • Hematology
  • Cell Biology
  • Immunology

Background:

  • Leukaemia inhibitory factor (LIF) is crucial for hematopoietic cell growth and differentiation.
  • Understanding the source and regulation of LIF in the bone marrow microenvironment is essential.

Purpose of the Study:

  • To investigate whether human bone marrow stromal cells produce LIF.
  • To identify factors that regulate LIF synthesis in these cells.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) was used to quantify human LIF.
  • Stromal cells were stimulated with various cytokines and agents, including lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), and specific interleukins.
  • Protein kinase C (PKC) dependency was assessed using specific inhibitors.

Main Results:

  • Human bone marrow stromal cells were confirmed to produce LIF.
  • LIF synthesis was dose-dependently enhanced by LPS and PMA.
  • PMA-induced LIF production was dependent on PKC, as shown by inhibition with sphingosine and staurosporine.
  • Several cytokines, including IL-1α, IL-1β, IL-3, IL-6, IL-8, TNF-α, and SCF, stimulated LIF production.
  • M-CSF, G-CSF, GM-CSF, bFGF, PAF, PGE2, LTB4, and LTC4 did not stimulate LIF production.

Conclusions:

  • Human bone marrow stromal cells are a significant source of LIF.
  • LIF production by stromal cells is regulated by various cytokines and signaling pathways, including PKC.
  • These findings highlight the role of stromal cells in cytokine-mediated LIF production within the bone marrow.

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