NADPH and Xanthine Oxidases Control Induction of Inflammatory Mediator Expression by Organic Dust in the Lung

Details

• Personal Author:
  Boggaram V ; Hamilton CE ; Keshava S ; Meganathan V ; Natarajan K
• Description:
  Exposure to organic dust in animal and agricultural farms and the ensuing lung inflammation are linked to the development of respiratory diseases. We found previously that elevated production of reactive oxygen species (ROS) by aqueous poultry organic dust extract (hereafter referred to as dust extract) mediates induction of proinflammatory mediators in airway epithelial cells. In the present study, we investigated whether ROS generated by NADPH oxidases (NOX) and xanthine oxidase (XO) controls induction of inflammatory mediators by dust extract and the underlying mechanisms in bronchial epithelial cells. Using chemical inhibitors and siRNA targeted knockdown, we found that NOX1, NOX2, NOX4, and XO-derived ROS regulates induction of proinflammatory mediator levels. Like airway epithelial cells in vitro, NOX inhibitor VAS2870 reduced keratinocyte chemoattractant (KC), IL-6, and TNF-a production and 4-hydroxynonenal (4-HNE) staining induced by dust extract in mouse lungs. VAS2870 inhibition of proinflammatory mediators was associated with reduced NF?B and Stat3 activation indicating that NOX generated ROS activates NF?B and Stat3 to induce proinflammatory gene expression. Dust extract increased the membrane association of p47phox in airway epithelial cells indicating NOX2 activation but had no effect on NOX2 protein levels. In summary, our studies have shown that NOX and XO generated ROS control organic dust induction of proinflammatory mediators in airway epithelial cells via NFkB and Stat3 activation. [Description provided by NIOSH]
• Subjects:
  Agriculture Animals Dust Farmers Food Industry Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Cytokines; Gene Regulation; Occupational Lung Diseases; Oxidative Stress Organic Dusts; Agriculture; Agricultural Industry; Farm Workers; Farmers; Poultry; In Vitro Study; Animals; Proteins; Oxidative Stress; Cytokines; Lung Disease;
• DOI:
  https://doi.org/10.1096/fj.202100732r
• ISSN:
  0892-6638
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 6 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  36
• Issue:
  7
• NIOSHTIC Number:
  nn:20065353
• Citation:
  FASEB J 2022 Jul; 36(7):e22381
• Contact Point Address:
  Vijay Boggaram, Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154
• Email:
  vijay.boggaram@uthct.edu
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Texas Health Center at Tyler
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  The FASEB Journal
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6132a98f0da03bf2c5b1177300596ed8f234ffecb2e95d2652200d21f54eb83de5a5a28f06859fdbf9d853652882e658cb96ef8dce8a25d984ca87706145260d
• Download URL:
  https://stacks.cdc.gov/view/cdc/248914/cdc_248914_DS1.pdf
• File Type:
  [PDF - 40.92 MB ]