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Innate Immune Pathways Associated with Lung Radioprotection by Soy Isoflavones.

Lisa M Abernathy1, Matthew D Fountain2, Michael C Joiner3

  • 1Department of Oncology, Division of Radiation Oncology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Microbiology and Immunology, Indiana University School of Medicine at Notre Dame, South Bend, IN, USA.

Frontiers in Oncology
|February 8, 2017
PubMed
Summary

Soy isoflavones protect lungs from radiation injury by promoting arginase-1 expressing myeloid-derived suppressor cells. This mechanism may involve suppressing inflammation and protecting lung tissue from radiation damage.

Keywords:
MDSCsarginase-1lung inflammationradiationsoy isoflavones

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Area of Science:

  • Oncology
  • Radiology
  • Immunology

Background:

  • Radiation therapy for lung cancer can cause lung injury, including pneumonitis and fibrosis.
  • Soy isoflavones show potential in protecting against radiation-induced lung injury, but the underlying mechanisms are not fully understood.
  • This study investigates the role of myeloid-derived suppressor cells (MDSCs) and their modulation by soy isoflavones in lung radioprotection.

Purpose of the Study:

  • To investigate the effect of radiation on lung MDSCs.
  • To determine if soy isoflavones can modulate radiation-induced changes in MDSCs.
  • To explore the potential role of MDSCs and soy isoflavones in mitigating radiation-induced lung injury.

Main Methods:

  • BALB/c mice received thoracic irradiation and daily soy isoflavone supplementation.
  • Western blot and immunohistochemistry were used to detect arginase-1 (Arg-1) and nuclear factor κB (NF-κB) p65 in lung tissue.
  • Flow cytometry analyzed lung MDSC subsets and Arg-1 expression, while ELISA measured cytokine levels.

Main Results:

  • Radiation decreased Arg-1 expressing cells in the lungs, but soy isoflavones maintained these cells.
  • Arg-1 was primarily expressed in granulocytic MDSCs (gr-MDSCs), and its expression was reduced by radiation but preserved by soy isoflavones.
  • Soy isoflavones increased Arg-1+ cells, inhibited radiation-induced NF-κB activation, and controlled pro-inflammatory cytokine production.

Conclusions:

  • Soy isoflavones may offer radioprotection by promoting Arg-1-expressing gr-MDSCs.
  • This promotion of gr-MDSCs by soy isoflavones could downregulate inflammation.
  • The findings suggest a novel mechanism for soy isoflavones in lung radioprotection.