Peroxisome Proliferator-Activated Receptor Gamma (PPAR-Y) Activator 15d-PGJ2 Suppresses Organic Dust Induction of Lung Inflammatory Mediators Independently of PPAR-y

Details

• Personal Author:
  Boggaram V ; Kusampudi S ; Meganathan V ; Nsiah P
• Description:
  Background: Long-term exposure to organic dust is associated with chronic lung inflammation and development of respiratory diseases. Peroxisome proliferator-activated receptor gamma (PPAR-y), a transcription factor belonging to the nuclear hormone receptor family has been reported to modulate inflammatory responses in several organs including lung. In this study, we hypothesized that activation of PPAR-y modulates organic dust induced lung inflammation. Methods: Settled poultry farm dust was extracted with D-PBS to prepare dust extract. The effects of PPAR-y agonists, 15-Deoxy-Delta-12,14-prostaglandin J2 (15d-PGJ2), Rosiglitazone, and GW1929 on inflammatory gene expression in Beas2B bronchial epithelial cells and THP-1 macrophages were analyzed by real time qRT-PCR, ELISA, and western blotting. Effects on cell toxicity were determined by MTS assay. Cellular reactive oxygen species (ROS) levels were measured by 2',7'-dichlorofluorescein diacetate (DCFDA) labeling. NF-kB and STAT-3 activation was analyzed by western blotting. Results: Among the PPAR-y agonists tested, 15d-PGJ2 potently inhibited dust extract induction of pro-IL1β, ICAM-1, IL-6 and IL-8 proteins, whereas Rosiglitazone and GW1929 did not. Inhibitions of IL-1β, ICAM-1, IL-6 and IL-8 proteins were found to be due to reduced mRNA expression. 15d-PGJ2 inhibited ROS production and NF-kB and STAT-3 activation. MTS assay showed that 15d-PGJ2 did not cause cell toxicity. PPAR-y antagonists and siRNA knock down of PPAR-y had no effect on dust extract induction of inflammatory mediators. Conclusion: Our data has indicated that 15d-PGJ2 suppresses organic dust induced lung inflammatory mediators independentenly of PPAR-y activation. 15d-PGJ2 suppression of inflammatory mediators may be due to inhibition of ROS production and NF-kB and STAT-3 activation. [Description provided by NIOSH]
• Subjects:
  Dust Occupational Health Safety
• Keywords:
  Chronic Inflammation Dust Inhalation Gene Expression Organic Dusts Reactive Oxygen Species ROS
• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 6 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  209
• NIOSHTIC Number:
  nn:20070062
• Citation:
  Am J Respir Crit Care Med 2024 May; 209(Abstract Issue):A4414
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Texas Health Center at Tyler
• Peer Reviewed:
  False
• Start Date:
  20010930
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f44a1285bf0755fce1322916e249f2d3561f1973206a816baf75f7f9802ada58b421093bc3503d232d5dc7f75b5a9c1d3c198beff5acce5c3fd830ca146885c7
• Download URL:
  https://stacks.cdc.gov/view/cdc/208360/cdc_208360_DS1.pdf
• File Type:
  [PDF - 24.79 KB ]