Dimethylarginine dimethylaminohydrolase (DDAH) overexpression attenuates agricultural organic dust-injured airway epithelial wound repair

Details

• Personal Author:
  Poole JA ; Romberger DJ ; Staab EB ; Sweeter JM ; Wyatt TA
• Description:
  Introduction: Inhalation of dusts from confined animal feeding operations (CAFO), which contain microbial components, is associated with bronchitis, asthma, and chronic obstructive pulmonary disease (COPD). Such diseases lead to chronic inflammation and remodeling of the airways. Proper airway epithelial wound repair represents an important safeguard against aberrant lung remodeling. Agents that activate cAMP-dependent protein kinase (PKA) enhance wound repair while agents that activate protein kinase C (PKC) inhibit wound repair. Previously, we have reported that bronchial epithelial cell exposure to swine CAFO dust significantly blunts normative cell migration and wound repair via a PKC-dependent mechanism. In addition, we have shown that agents blocking nitric oxide (NO) production prevent the activation of PKA in airway epithelium. Therefore, we hypothesized that blocking an endogenous NO inhibitor would mitigate the effects of swine CAFO dust on epithelial wound repair. Methods: To test this hypothesis, we cultured primary tracheal epithelial cells in monolayers from both wild type and dimethylarginine dimethylaminohydrolase (DDAH) overexpressing C57Bl/6 mice and measured wound repair using the electric cell impedance sensing (ECIS) system. Results: Migration of epithelial cell monolayers from wild type mice significantly promoted repair of the ECIS-standardized wound as determined by resistance. In contrast, pretreatment of the wild type cell monolayers with 5% swine CAFO dust extract for 1 hr required approximately 5-6 hr longer to achieve an equivalent repair response vs. control media and 24 hr dust pretreatment nearly abrogated all repair. In cells from DDAH overexpressing mice, wounds were repaired up to 8 hr earlier than wild type mice. Importantly, a significant enhancement of wound repair (25% increase in resistance) was observed in DDAH cells vs. wild type cells treated with swine CAFO dust for 24 hr. Conclusions: These data suggest that preserving the NO signal through endogenous inhibition of asymmetric dimethylarginine (the endogenous nitric oxide inhibitor) enhances wound repair even in the presence of swine dust exposure. The targeting of NO may represent a future strategy to address dust-induced chronic lung injury. [Description provided by NIOSH]
• Subjects:
  Agriculture Animal Husbandry Animals Asthma Asthma, Occupational Cells, Cultured Dust Immune System Laboratories Lung Microbiology Nitric Oxide Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Agricultural Industry Agricultural Workers Airway Obstruction Animal Husbandry Animal Husbandry Workers Bronchial Asthma Cell Cultures Cell Culture Techniques Cell Migration Cell Signaling Cell Type Cellular Effects Cellular Reactions Chemical Inhibition Chronic Inflammation Chronic Obstructive Pulmonary Disease COPD Dusts Enzyme Inhibitors Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Cells Microorganisms Nitric Oxide Occupational Asthma Organic Dusts Proteins Respiratory System Disorders

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• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  191
• NIOSHTIC Number:
  nn:20048522
• Citation:
  Am J Respir Crit Care Med 2015 May; 191(Abstract Issue):A2587
• Contact Point Address:
  T. A. Wyatt, University of Nebraska Medical Center, Omaha, NE
• Email:
  twyatt@unmc.edu
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  False
• Start Date:
  20110901
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4d8bf04dc691f87f9f7a5d32c26edbb987899f4b66ef56fd4d41e136d16e8949777a1e4bf64025c98d0609983c94a9985d6767c48cca09cf7feb264904a90e78
• Download URL:
  https://stacks.cdc.gov/view/cdc/203262/cdc_203262_DS1.pdf
• File Type:
  [PDF - 17.55 KB ]