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Sphingosine modulates interleukin-6 synthesis in osteoblasts

O Kozawa1, H Tokuda, H Matsuno

  • 1Department of Pharmacology, Gifu University School of Medicine, Japan.

Journal of Cellular Biochemistry
|August 26, 1998
PubMed
Summary

Sphingosine modulates interleukin-6 (IL-6) synthesis in osteoblasts. It inhibits IL-6 induced by various factors but enhances tumor necrosis factor-alpha (TNF)-induced IL-6, suggesting complex regulatory roles.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Osteology

Background:

  • Prostaglandins (PGE1, PGF2alpha), bFGF, and TNF-alpha are known inducers of interleukin-6 (IL-6) in osteoblast-like MC3T3-E1 cells.
  • These signaling pathways involve protein kinase A (PKA), protein kinase C (PKC), intracellular calcium (Ca2+), and sphingosine 1-phosphate.
  • Sphingomyelin metabolites, including sphingosine, are implicated in cellular signaling.

Purpose of the Study:

  • To investigate the role of sphingosine, a sphingomyelin metabolite, in regulating IL-6 synthesis in MC3T3-E1 osteoblasts.
  • To determine how sphingosine affects IL-6 production stimulated by various agonists acting through different signaling pathways.

Main Methods:

  • MC3T3-E1 cells were treated with various agonists known to induce IL-6 synthesis.

Related Experiment Videos

  • The effect of exogenous sphingosine on agonist-induced IL-6 production was assessed.
  • The impact of DL-threo-dihydrosphingosine, a sphingosine kinase inhibitor, on TNF-alpha-induced IL-6 and sphingosine's effect was evaluated.

    • Main Results:

    • Sphingosine inhibited IL-6 synthesis induced by PGF2alpha, 12-O-tetradecanoylphorbol-13-acetate (PKC activator), PGE1, cholera toxin, forskolin, dibutyryl cAMP (PKA pathway activators), bFGF, and A23187 (Ca2+ mobilizer).
    • Sphingosine did not affect IL-6 synthesis induced by interleukin-1.
    • Sphingosine enhanced TNF-alpha-induced IL-6 synthesis, an effect partially reduced by DL-threo-dihydrosphingosine.

    Conclusions:

    • Sphingosine plays a significant role in modulating IL-6 synthesis in osteoblasts, acting as an inhibitor for most tested agonists.
    • The observed enhancement of TNF-alpha-induced IL-6 by sphingosine, and its partial reversal by a sphingosine kinase inhibitor, suggests a complex, potentially pathway-specific, regulatory mechanism.
    • These findings highlight sphingosine as a key modulator in osteoblast inflammatory signaling.