Myeloid differentiation factor 88-dependent signaling is critical for acute organic dust-induced airway inflammation in mice

Details

• Personal Author:
  Bauer C ; Gleason AM ; Kielian T ; Poole JA ; Romberger DJ ; West WW ; Wyatt TA
• Description:
  Organic dust exposure within agricultural environments results in airway diseases. Toll-like receptor 2 (TLR2) and TLR4 only partly account for the innate response to these complex dust exposures. To determine the central pathway in mediating complex organic dust-induced airway inflammation, this study targeted the common adaptor protein, myeloid differentiation factor 88 (MyD88), and investigated the relative contributions of receptors upstream from this adaptor. Wild-type, MyD88, TLR9, TLR4, IL-1 receptor I (RI), and IL-18R knockout (KO) mice were challenged intranasally with organic dust extract (ODE) or saline, according to an established protocol. Airway hyperresponsiveness (AHR) was assessed by invasive pulmonary measurements. Bronchoalveolar lavage fluid was collected to quantitate leukocyte influx and cytokine/chemokine (TNF-a, IL-6, chemokine [C-X-C motif] ligands [CXCL1 and CXCL2]) concentrations. Lung tissue was collected for histopathology. Lung cell apoptosis was determined by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and lymphocyte influx and intercellular adhesion molecule-1 (ICAM-1) expression were assessed by immunohistochemistry. ODE-induced AHR was significantly attenuated in MyD88 KO mice, and neutrophil influx and cytokine/chemokine production were nearly absent in MyD88 KO animals after ODE challenges. Despite a near-absent airspace inflammatory response, lung parenchymal inflammation was increased in MyD88 KO mice after repeated ODE exposures. ODE-induced epithelial-cell ICAM-1 expression was diminished in MyD88 KO mice. No difference was evident in the small degree of ODE-induced lung-cell apoptosis. Mice deficient in TLR9, TLR4, and IL-18R, but not IL-1IR, demonstrated partial protection against ODE-induced neutrophil influx and cytokine/chemokine production. Collectively, the acute organic dust-induced airway inflammatory response is highly dependent on MyD88 signaling, and is dictated, in part, by important contributions from upstream TLRs and IL-18R. [Description provided by NIOSH]
• Subjects:
  Agriculture Dust Energy Metabolism Environmental Exposure Laboratories Lung Occupational Health Pathology Respiratory System Safety
• Keywords:
  Analytical-processes Author Keywords: MyD88 Dust-particles Environmental-exposure IL-1R/IL-18R Laboratory-animals Metabolism Organic-dusts Organic Dust Proteins Toll-like Receptor

  More +
• ISSN:
  1044-1549
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• 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
• Volume:
  48
• Issue:
  6
• NIOSHTIC Number:
  nn:20043020
• Citation:
  Am J Respir Cell Mol Biol 2013 Jun; 48(6):781-789
• Contact Point Address:
  Jill A. Poole, M.D., Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Medicine, University of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Start Date:
  20060801
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a456880205d413022008beaa70bf4ceed8a342adbe1e4a48237f3a362378247e41f53e0e755e0be30fac980a084a0e347475ee83870158e64577dde62c7fc68d
• Download URL:
  https://stacks.cdc.gov/view/cdc/195051/cdc_195051_DS1.pdf
• File Type:
  [PDF - 1.86 MB ]