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Interleukin-1 beta induces the expression and production of stem cell factor by epithelial cells: crucial involvement of the PI-3K/mTOR pathway and HIF-1 transcription complex

Cellular & Molecular Immunology volume 13, pages 47–56 (2016)Cite this article

Abstract

Potential crosslinks between inflammation and leukaemia have been discussed for some time, but experimental evidence to support this dogma is scarce. In particular, it is important to understand the mechanisms responsible for potential upregulation of proto-oncogenic growth factor expressions by inflammatory mediators. Here, we investigated the ability of the highly inflammatory cytokine interleukin-1 beta (IL-1β) to induce the production of stem cell factor (SCF), which is a major hematopoietic growth factor that controls the progression of acute myeloid leukaemia upon malignant transformation of haematopoietic myeloid cells. We found that human IL-1β induced the expression/secretion of SCF in MCF-7 human epithelial breast cancer cells and that this process depended on the hypoxia-inducible factor 1 (HIF-1) transcription complex. We also demonstrated a crucial role of the phosphatidylinositol-3 kinase (PI-3K)/mammalian target of rapamycin (mTOR) pathway in IL-1β-induced HIF-1α accumulation in MCF-7 cells. Importantly, mTOR was also found to play a role in IL-1β-induced SCF production. Furthermore, a tendency for a positive correlation of IL-1β and SCF levels in the plasma of healthy human donors was observed. Altogether, our results demonstrate that IL-1β, which normally bridges innate and adaptive immunity, induces the production of the major haematopoietic/proleukaemic growth factor SCF through the PI-3K/mTOR pathway and the HIF-1 transcription complex. These findings strongly support a cross-talk between inflammation and acute myeloid leukaemia.

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Author notes

  1. Rafal W Wyszynski and Bernhard F Gibbs: These authors are contributed equally to this study.

Authors and Affiliations

  1. School of Pharmacy, University of Kent, Kent, UK

    Rafal W Wyszynski, Bernhard F Gibbs & Vadim V Sumbayev

  2. Institute for Research in Biomedicine, Bellinzona, Switzerland

    Luca Varani & Daniela Iannotta

Authors
  1. Rafal W Wyszynski
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  2. Bernhard F Gibbs
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  3. Luca Varani
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  4. Daniela Iannotta
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  5. Vadim V Sumbayev
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Correspondence to Bernhard F Gibbs or Vadim V Sumbayev.

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Wyszynski, R., Gibbs, B., Varani, L. et al. Interleukin-1 beta induces the expression and production of stem cell factor by epithelial cells: crucial involvement of the PI-3K/mTOR pathway and HIF-1 transcription complex. Cell Mol Immunol 13, 47–56 (2016). https://doi.org/10.1038/cmi.2014.113

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