Maresin-1 Reduces the Pro-Inflammatory Response of Bronchial Epithelial Cells to Organic Dust

Details

• Journal Article:
  Respir Res
• Personal Author:
  Nordgren, Tara M. ; Heires, Art J. ; Wyatt, Todd A. ; Poole, Jill A. ; LeVan, Tricia D. ; Cerutis, D. Roselyn ; Romberger, Debra J.
• Description:
  Background
  
  Exposure to organic dust causes detrimental airway inflammation. Current preventative and therapeutic measures do not adequately treat resulting disease, necessitating novel therapeutic interventions. Recently identified mediators derived from polyunsaturated fatty acids exhibit anti-inflammatory and pro-resolving actions. We tested the potential of one of these mediators, maresin-1 (MaR1), in reducing organic dust-associated airway inflammation.
  
  Methods
  
  As bronchial epithelial cells (BECs) are pivotal in initiating organic dust-induced inflammation, we investigated the in vitro effects of MaR1 on a human BEC cell line (BEAS-2B). Cells were pretreated for 1 hour with 0–200 nM MaR1, followed by 1–24 hour treatment with 5% hog confinement facility-derived organic dust extract (HDE). Alternatively, a mouse lung slice model was utilized in supportive cytokine studies. Supernatants were harvested and cytokine levels determined via enzyme-linked immunosorbent assays. Epithelial cell protein kinase C (PKC) isoforms α and ϵ, and PKA activities were assessed via radioactivity assays, and NFκB and MAPK-related signaling mechanisms were investigated using luciferase vector reporters.
  
  Results
  
  MaR1 dose-dependently reduced IL-6 and IL-8 production following HDE treatment of BECs. MaR1 also reduced HDE-stimulated cytokine release including TNF-α in a mouse lung slice model when given before or following HDE treatment. Previous studies have established that HDE sequentially activates epithelial PKCα and PKCϵ at 1 and 6 hours, respectively that regulated TNF-α, IL-6, and IL-8 release. MaR1 pretreatment abrogated these HDE-induced PKC activities. Furthermore, HDE treatment over a 24-hour period revealed temporal increases in NFκB, AP-1, SP-1, and SRE DNA binding activities, using luciferase reporter assays. MaR1 pretreatment did not alter the activation of NFκB, AP-1, or SP-1, but did reduce the activation of DNA binding at SRE.
  
  Conclusions
  
  These observations indicate a role for MaR1 in attenuating the pro-inflammatory responses of BECs to organic dust extract, through a mechanism that does not appear to rely on reduced NFκB, AP-1, or SP-1-related signaling, but may be mediated partly through SRE-related signaling. These data offer insights for a novel mechanistic action of MaR1 in bronchial epithelial cells, and support future in vivo studies to test MaR1’s utility in reducing the deleterious inflammatory effects of environmental dust exposures.
  
  
• Subjects:
  Animals Anti-Inflammatory Agents Bronchitis Cytokines Docosahexaenoic Acids Dust Epithelial Cells In Vitro Techniques Mice Mice, Inbred C57BL Respiratory System Respiratory Tract Diseases Transcription Factors

  More +
• Keywords:
  Author Keywords: Maresin-1; Pro-resolving Mediators; Organic Dust Exposures; Airway Inflammation; Bronchial Epithelial Cells Organic-dusts; Organic-compounds; Airway-obstruction; Preventive-medicine; Therapeutic-agents; Cell-function; Cell-biology; Cellular-function; Laboratory-animals;
• Source:
  Respir Res. 2013; 14(1):51.
• Pubmed ID:
  23663457
• Pubmed Central ID:
  PMC3668181
• Document Type:
  Text
• Funding:
  F32 ES022913/ES/NIEHS NIH HHS/United States ; R01 ES019325/ES/NIEHS NIH HHS/United States ; R01AA017993/AA/NIAAA NIH HHS/United States ; R01ES019325/ES/NIEHS NIH HHS/United States ; R01OH008539/OH/NIOSH CDC HHS/United States ; U54OH010162/OH/NIOSH CDC HHS/United States
• 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:
  10 pdf pages
• Volume:
  14
• NIOSHTIC Number:
  nn:20046026
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Collection(s):
  CDC Public Access National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fec0b9204ff5c89802c5dd1089484a2b053d52981dd893e88828c3b3dde263112119b8fde68b6ed48efdb3ec2422eeca5fe09a6c827c3cfc75594fcded545cfe
• Download URL:
  https://stacks.cdc.gov/view/cdc/32124/cdc_32124_DS1.pdf
• File Type:
  [PDF - 410.83 KB ]