Sex Differences Impact the Lung-Bone Inflammatory Response to Repetitive Inhalant Lipopolysaccharide Exposures in Mice

Details

• Personal Author:
  Janike K ; Mikuls TR ; Nelson AJ ; Poole JA ; Romberger DJ ; Roy SK ; Swanson B ; Thiele GM ; Wang D ; Warren K
• Description:
  Skeletal health consequences associated with inflammatory diseases of the airways significantly contribute to morbidity. Sex differences have been described independently for lung and bone diseases. Repetitive inhalant exposure to lipopolysaccharide (LPS) induces bone loss and deterioration in male mice, but comparison effects in females are unknown. Using an intranasal inhalation exposure model, 8-week-old C57BL/6 male and female mice were treated daily with LPS (100 ng) or saline for 3 weeks. Bronchoalveolar lavage fluids, lung tissues, tibias, bone marrow cells, and blood were collected. LPS-induced airway neutrophil influx, interleukin (IL)-6 and neutrophil chemoattractant levels, and bronchiolar inflammation were exaggerated in male animals as compared to female mice. Trabecular bone micro-CT imaging and analysis of the proximal tibia were conducted. Inhalant LPS exposures lead to deterioration of bone quality only in male mice (not females) marked by decreased bone mineral density, bone volume/tissue volume ratio, trabecular thickness and number, and increased bone surface-to-bone volume ratio. Serum pentraxin-2 levels were modulated by sex differences and LPS exposure. In proof-of-concept studies, ovarectomized female mice demonstrated LPS-induced bone deterioration, and estradiol supplementation of ovarectomized female mice and control male mice protected against LPS-induced bone deterioration findings. Collectively, sex-specific differences exist in LPS-induced airway inflammatory consequences with significant differences found in bone quantity and quality parameters. Male mice demonstrated susceptibility to bone loss and female animals were protected, which was modulated by estrogen. Therefore, sex differences influence the biologic response in the lung-bone inflammatory axis in response to inhalant LPS exposures. [Description provided by NIOSH]
• Subjects:
  Estrogens Immune System Laboratories Lipids Lung Lung Diseases Occupational Health Radiography Respiratory System Respiratory Tract Diseases Safety Sex Characteristics

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• Keywords:
  Airway Resistance Author Keywords: Osteoporosis Biological Effects Bone Density Bone Disorders Bone Marrow Exposure Assessment Immune Reaction Inflammatory Lung Disease Inhalation Laboratory Animals Lipopolysaccharide Lung Disorders Micro-CT Imaging Neutrophils Sex Factors X-ray Analysis

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• ISSN:
  1547-691X
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  73-81
• Volume:
  15
• Issue:
  1
• NIOSHTIC Number:
  nn:20052845
• Citation:
  J Immunotoxicol 2018 Dec; 15(1):73-81
• Contact Point Address:
  Jill A. Poole, Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, 985990 Nebraska Medical Center, Omaha, NE 68198-5990, USA
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Journal of Immunotoxicology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8af14baf2d9fa5953773d07d1951b9f6e0e617311b4ac8d3a5072243932eeff98c7d87af2b6e746b1fc556416d8b6710d0662cc0b4dfe9d45d9d121645ec79fd
• Download URL:
  https://stacks.cdc.gov/view/cdc/215765/cdc_215765_DS1.pdf
• File Type:
  [PDF - 1.52 MB ]