Amphiregulin Modulates Murine Lung Recovery and Fibroblast Function Following Exposure to Agriculture Organic Dust

Details

• Personal Author:
  Bailey KL ; Heires AJ ; Katafiasz D ; Nelson AJ ; Nordgren TM ; Poole JA ; Romberger DJ
• Description:
  Exposure to agricultural bioaerosols can lead to chronic inflammatory lung diseases. Amphiregulin (AREG) can promote the lung repair process but can also lead to fibrotic remodeling. The objective of this study was to determine the role of AREG in altering recovery from environmental dust exposure in a murine in vivo model and in vitro using cultured human and murine lung fibroblasts. C57BL/6 mice were intranasally exposed to swine confinement facility dust extract (DE) or saline daily for 1 wk or allowed to recover for 3-7 days while being treated with an AREG-neutralizing antibody or recombinant AREG. Treatment with the anti-AREG antibody prevented resolution of DE exposure-induced airway influx of total cells, neutrophils, and macrophages and increased levels of TNF-a, IL-6, and CXCL1. Neutrophils and activated macrophages (CD11c+ CD11bhi) persisted after recovery in lung tissues of anti-AREG-treated mice. In murine and human lung fibroblasts, DE induced the release of AREG and inflammatory cytokines. Fibroblast recellularization of primary human lung mesenchymal matrix scaffolds and wound closure was inhibited by DE and enhanced with recombinant AREG alone. AREG treatment rescued the DE-induced inhibitory fibroblast effects. AREG intranasal treatment for 3 days during recovery phase reduced repetitive DE-induced airway inflammatory cell influx and cytokine release. Collectively, these studies demonstrate that inhibition of AREG reduced, whereas AREG supplementation promoted, the airway inflammatory recovery response following environmental bioaerosol exposure, and AREG enhanced fibroblast function, suggesting that AREG could be targeted in agricultural workers repetitively exposed to organic dust environments to potentially prevent and/or reduce disease. [Description provided by NIOSH]
• Subjects:
  Agriculture Antibodies Blood Dust Immune System Lung Macrophages Occupational Health Respiratory System Safety
• Keywords:
  Amphiregulin Antibody Response Author Keywords: Agriculture Bioaerosols Chronic Inflammation Cytokines Dust Dust Exposure Exposure Assessment Fibroblast Fibroblasts Immune Reaction Inflammation Lung Lung Cells Lung Tissue Neutrophils Organic Dusts Recovery Repair

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Nebraska ; OSHA Region 7 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  318
• Issue:
  1
• NIOSHTIC Number:
  nn:20059528
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2020 Jan; 318(1):L180-L191
• Contact Point Address:
  J. A. Poole, 985990 Nebraska Medical Center, Omaha, NE 68198-5990
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:889fcec971d06fed6281ba45127435e30d7aae00fe7a3c63ba4b2e0a5dc839ed8cd06c2499274286e487710424deec49cab02d0cfad5d4aba58ab139a013158a
• Download URL:
  https://stacks.cdc.gov/view/cdc/223725/cdc_223725_DS1.pdf
• File Type:
  [PDF - 2.07 MB ]