Dimethylarginine Dimethylaminohydrolase (DDAH) Overexpression Enhances Wound Repair in Airway Epithelial Cells Exposed to Agricultural Organic Dust

Details

• Personal Author:
  Bailey KL ; Chandra D ; DeVasure JM ; Poole JA ; Romberger DJ ; Staab E ; Sweeter JM ; Wyatt TA
• Description:
  Objective: Workers exposed to dusts from concentrated animal feeding operations have a high prevalence of pulmonary diseases. These exposures lead to chronic inflammation and aberrant airway remodeling. Previous work shows that activating cAMP-dependent protein kinase (PKA) enhances airway epithelial wound repair while activating protein kinase C (PKC) inhibits wound repair. Hog barn dust extracts slow cell migration and wound repair via a PKC-dependent mechanism. Further, blocking nitric oxide (NO) production in bronchial epithelial cells prevents PKA activation. We hypothesized that blocking an endogenous NO inhibitor, asymmetric dimethylarginine, by overexpressing dimethylarginine dimethylaminohydrolase mitigates the effects of hog dust extract on airway epithelial would repair. Materials/methods: We cultured primary tracheal epithelial cells in monolayers from both wild-type (WT) and dimethylarginine dimethylaminohydrolase overexpressing C57Bl/6 (DDAH1 transgenic) mice and measured wound repair using the electric cell impedance sensing system. Results: Wound closure in epithelial cells from WT mice occurred within 24 h in vitro. In contrast, treatment of the WT cell monolayers with 5% hog dust extract prevented significant NO-stimulated wound closure. In cells from DDAH1 transgenic mice, control wounds were repaired up to 8 h earlier than seen in WT mice. A significant enhancement of wound repair was observed in DDAH cells compared to WT cells treated with hog dust extract for 24 h. Likewise, cells from DDAH1 transgenic mice demonstrated increased NO and PKA activity and decreased hog dust extract-stimulated PKC. Discussion/conclusion: Preserving the NO signal through endogenous inhibition of asymmetric dimethylarginine enhances wound repair even in the presence of dust exposure. [Description provided by NIOSH]
• Subjects:
  Agriculture Animals Dust Laboratories Lung Diseases Nitric Oxide Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Epithelial Wound Repair Cell Type Dimethylarginine Dimethylaminohydrolase In Vitro Study Laboratory Animals Nitric Oxide Organic Dusts Protein Kinase C Proteins Pulmonary System Disorders Respiratory System Disorders

  More +
• ISSN:
  0895-8378
• 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:
  133-139
• Volume:
  30
• Issue:
  3
• NIOSHTIC Number:
  nn:20053212
• Citation:
  Inhal Toxicol 2018 Feb; 30(3):133-139
• Contact Point Address:
  Todd A. Wyatt, Pulmonary, Critical Care, Sleep and Allergy Division; Department of Internal Medicine, University of Nebraska Medical Center, 985910 The Nebraska Medical Center, Omaha, NE 68198-5910
• Email:
  twyatt@unmc.edu
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Inhalation Toxicology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:830430b01964f372a318702ae5748348d5f69a74e8b540d9d5e77be33c08f4de1f973953d2aca445d85e048261e80f7a781c8ceac9898eafdd6ebd9a00d583f3
• Download URL:
  https://stacks.cdc.gov/view/cdc/216015/cdc_216015_DS1.pdf
• File Type:
  [PDF - 1.28 MB ]