title: Soy Isoflavones Promote Radioprotection of Normal Lung Tissue by Inhibition of Radiation-Induced Activation of Macrophages and Neutrophils.
abstract: BACKGROUND
  Radiation therapy for lung cancer is limited by toxicity to normal lung tissue that results from an inflammatory process, leading to pneumonitis and fibrosis. Soy isoflavones mitigate inflammatory infiltrates and radiation-induced lung injury, but the cellular immune mediators involved in the radioprotective effect are unknown.
  
  
  METHODS
  Mice received a single dose of 10 Gy radiation delivered to the lungs and daily oral treatment of soy isoflavones. At different time points, mice were either processed to harvest bronchoalveolar lavage fluid for differential cell counting and lungs for flow cytometry or immunohistochemistry studies.
  
  
  RESULTS
  Combined soy and radiation led to a reduction in infiltration and activation of alveolar macrophages and neutrophils in both the bronchoalveolar and lung parenchyma compartments. Soy treatment protected F4/80CD11c interstitial macrophages, which are known to play an immunoregulatory role and are decreased by radiation. Furthermore, soy isoflavones reduced the levels of nitric oxide synthase 2 expression while increasing arginase-1 expression after radiation, suggesting a switch from proinflammatory M1 macrophage to an anti-inflammatory M2 macrophage phenotype. Soy also prevented the influx of activated neutrophils in lung caused by radiation.
  
  
  CONCLUSIONS
  Soy isoflavones inhibit the infiltration and activation of macrophages and neutrophils induced by radiation in lungs. Soy isoflavones-mediated modulation of macrophage and neutrophil responses to radiation may contribute to a mechanism of resolution of radiation-induced chronic inflammation leading to radioprotection of lung tissue.
authors.affiliation: *Department of Immunology and Microbiology, †Division of Radiation Oncology, Department of Oncology, and ‡Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Abernathy
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Fountain
authors.forename: Shoshana E
authors.initials: SE
authors.lastname: Rothstein
authors.forename: John M
authors.initials: JM
authors.lastname: David
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Yunker
authors.forename: Joseph
authors.initials: J
authors.lastname: Rakowski
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.forename: Michael C
authors.initials: MC
authors.lastname: Joiner
authors.forename: Gilda G
authors.initials: GG
authors.lastname: Hillman
mesh_terms: D000818:Animals; D005260:Female; D007529:Isoflavones / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D008262:Macrophage Activation / Q000187:drug effects / Q000528:radiation effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry
chemical_list: D007529:Isoflavones; D011837:Radiation-Protective Agents