Dimethylarginine Dimethylaminohydrolase (DDAH) Overexpression Attenuates Agricultural Organic Dust Extract-Induced Inflammation

Details

• Journal Article:
  J Environ Immunol Toxicol
• Personal Author:
  Bailey, Kristina L. ; Wyatt, Todd A. ; Wells, S. M. ; Klein, E. B. ; Robinson, Jaimie E. ; Romberger, Debra J. ; Poole, Jill A. ; Bailey, Kristina L. ; Wyatt, Todd A. ; Wells, S. M. ; Klein, E. B. ; Robinson, Jaimie E. ; Romberger, Debra J. ; Poole, Jill A.
• Description:
  Modern, industrialized farming practices have lead to working conditions that include high levels of airborne dust. Agricultural workers inhale these complex organic dusts on a daily basis, leading to airway inflammation and higher risk for developing chronic obstructive pulmonary disease. The mechanisms regulating the organic dust-induced airway inflammatory response are not well-defined. We investigated whether overexpression of dimethylarginine dimethylaminohydrolase (DDAH) would lead to diminished pulmonary inflammation in an animal model of organic dust extract exposure. We instilled wild-type (WT) and DDAH overexpressing mice with an aqueous organic dust extract (ODE) collected from a swine confinement building. We found that inflammatory indices such as neutrophil influx and inflammatory cytokine production was lower in the DDAH overexpressing mice compared to WT after organic dust extract (ODE) instillation. We went on to determine how DDAH was mediating the decrease in inflammation induced by ODE. PKCα and PKCε play an essential role in the ODE inflammatory response. In a model of lung slices from WT and DDAH overexpressing mice, we demonstrated an increase in PKCα and PKCε in the WT mice exposed to ODE. This increase was diminished in the DDAH overexpressing mice exposed to ODE. We also tested an important component of the ODE, peptidoglycan (PGN). We noted a similar decrease in neutrophils and inflammatory cytokines in the DDAH overexpressing animals instilled with PGN compared to WT. In conclusion, our studies found a role for DDAH in regulating the ODE-triggered activation of epithelial PKCα and PKCε, a previously unrecognized mechanism of action. This ultimately results in diminished pulmonary inflammation.
• Subjects:
  Agriculture Dust Respiratory System Respiratory Tract Diseases
• Keywords:
  Agriculture; Organic Dusts; Pulmonary System Disorders; Respiratory System Disorders; Proteins; Nitric Oxide; Cell Type; Laboratory Animals; In Vitro Study; Author Keywords: Pulmonary; Lung; Inflammation; Swine Confinement Dust; Peptidoglycan; Asymmetric Dimethylarginine (ADMA); Nitric Oxide; CXCL-1; KC; CXCL-2; MIP1; IL-1beta; Precision Cut Lung Slices; PKCalpha; PKCepsilon; Neutrophils; Bronchoalveolar Lavage
• Source:
  J Environ Immunol Toxicol. 2(2):72-78. ; J Environ Immunol Toxicol. 2(2):72-78.
• Pubmed ID:
  25221746
• Pubmed Central ID:
  PMC4159103
• Document Type:
  Text
• Funding:
  R01 AA017993/AA/NIAAA NIH HHS/United States ; R01 OH008539/OH/NIOSH CDC HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; K08 AA019503/AA/NIAAA NIH HHS/United States ; R01 ES019325/ES/NIEHS NIH HHS/United States ; U54 OH010162/OH/NIOSH CDC HHS/United States
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  14 pdf pages
• Volume:
  2
• Issue:
  2
• NIOSHTIC Number:
  nn:20053858
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9) ; Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Agriculture, Forestry and Fishing ; Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Collection(s):
  National Institute for Occupational Safety and Health CDC Public Access
• Main Document Checksum:
  urn:sha-512:0c3c3bc19313a0d8a193213288a38dc7b312296ad5420dfeb47132ee92fe386d12d43994833814a65ff5c4ebac5599131df8e3858792b938634fbfd9520ab279
• Download URL:
  https://stacks.cdc.gov/view/cdc/41982/cdc_41982_DS1.pdf
• File Type:
  [PDF - 1.35 MB ]