Docosahexaenoic Acid Enhances Amphiregulin-Mediated Bronchial Epithelial Cell Repair Processes Following Organic Dust Exposure

Details

• Personal Author:
  Bailey KL ; Heires AJ ; Katafiasz DM ; Nordgren TM ; Romberger DJ ; Toews ML ; Wichman CS ; Bailey KL ; Heires AJ ; Katafiasz DM ; Nordgren TM ; Romberger DJ ; Toews ML ; Wichman CS
• Description:
  Injurious dust exposures in the agricultural workplace involve the release of inflammatory mediators and activation of epidermal growth factor receptor (EGFR) in the respiratory epithelium. Amphiregulin (AREG), an EGFR ligand, mediates tissue repair and wound healing in the lung epithelium. Omega-3 fatty acids such as docosahexaenoic acid (DHA) are also known modulators of repair and resolution of inflammatory injury. This study investigated how AREG, DHA, and EGFR modulate lung repair processes following dust-induced injury. Primary human bronchial epithelial (BEC) and BEAS-2B cells were treated with an aqueous extract of swine confinement facility dust (DE) in the presence of DHA and AREG or EGFR inhibitors. Mice were exposed to DE intranasally with or without EGFR inhibition and DHA. Using a decellularized lung scaffolding tissue repair model, BEC recolonization of human lung scaffolds was analyzed in the context of DE, DHA, and AREG treatments. Through these investigations, we identified an important role for AREG in mediating BEC repair processes. DE-induced AREG release from BEC, and DHA treatment following DE exposure, enhanced this release. Both DHA and AREG also enhanced BEC repair capacities and rescued DE-induced recellularization deficits. In vivo, DHA treatment enhanced AREG production following DE exposure, whereas EGFR inhibitor-treated mice exhibited reduced AREG in their lung homogenates. These data indicate a role for AREG in the process of tissue repair after inflammatory lung injury caused by environmental dust exposure and implicate a role for DHA in regulating AREG-mediated repair signaling in BEC. [Description provided by NIOSH]
• Subjects:
  Agriculture Dust Growth Immune System Lung Occupational Health Respiratory System Safety
• Keywords:
  Agricultural Workers Author Keywords: Amphiregulin Bronchial Epithelial Cells Dust Exposure Fatty Acids Glycoproteins Growth Factors Immune Reaction Inflammation Lung Function Organic Dust Organic Dusts Proteins Repair Respiratory Health Respiratory Irritants

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  California ; Nebraska ; OSHA Region 7 ; OSHA Region 9
• 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
• Volume:
  314
• Issue:
  3
• NIOSHTIC Number:
  nn:20053856
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2018 Mar; 314(3):L421-L431
• Contact Point Address:
  Debra J. Romberger, Pulmonary, Critical Care, Sleep and Allergy Division, Deptartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198
• Email:
  dromberg@unmc.edu
• CAS Registry Number:
  Docosahexaenoic acid (CAS RN 25167-62-8) ; Docosahexaenoic acid (CAS RN 25167-62-8)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Agriculture, Forestry and Fishing ; 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 Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4351963ecc7d44a90c76b78eaa05fe4b47b3e671e5f2ec506faf3dab9eeb4be5786052b52934ba6408d5d9a2d49e927fe156759d0ded01fee1eb3f8681b1df68
• Download URL:
  https://stacks.cdc.gov/view/cdc/216544/cdc_216544_DS1.pdf
• File Type:
  [PDF - 893.96 KB ]