Organic Dust Induces Inflammatory Gene Expression in Lung Epithelial Cells via ROS-Dependent STAT-3 Activation

Details

• Personal Author:
  Boggaram V ; Meganathan V ; Mitchell C ; Natarajan K
• Description:
  Exposure to dust in agricultural and animal environments, known as organic dust, is associated with the development of respiratory symptoms and respiratory diseases. Inflammation is a key feature of lung pathologies associated with organic dust exposure, and exposure to organic dust induces the expression of several immune and inflammatory mediators. However, information on transcription factors and cellular and molecular mechanisms controlling the production of immune and inflammatory mediators induced by organic dust is limited. In this study, we have identified STAT-3 as an important transcription factor controlling the induction of expression of immune and inflammatory mediators by poultry dust extracts in airway epithelial cells and in mouse lungs and delineated the cellular pathway for STAT-3 activation. Poultry dust extract activated STAT-3 phosphorylation in Beas2B and normal human bronchial epithelial cells and in mouse lungs. Chemical inhibition and siRNA knockdown of STAT-3 suppressed induction of immune and inflammatory mediator expression. Antioxidants suppressed the increase of STAT-3 phosphorylation induced by poultry dust extract indicating that oxidative stress [elevated reactive oxygen species (ROS) levels] is important for the activation. Chemical inhibition and siRNA knockdown experiments demonstrated that STAT-3 activation is dependent on the activation of nonreceptor tyrosine-protein kinase 2 (TYK2) and epidermal growth factor receptor (EGFR) tyrosine kinases. Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator expression via a cellular pathway involving oxidative stress-mediated STAT-3 activation by TYK2 and EGFR tyrosine kinases. A corrigendum for this article has been published to correct Fig. 6A and is available here: https://doi.org/10.1152/ajplung.zh5-7683-corr.2019. [Description provided by NIOSH]
• Subjects:
  Agriculture Dust Food Handling Food Industry Immune System Occupational Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Cytokines Cellular Effects Cytokines Gene Regulation Immune Reaction Inflammation Occupational Diseases Occupational Lung Diseases Organic Dusts Oxidative Stress Poultry Industry Poultry Workers Respiratory Diseases

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• ISSN:
  1040-0605
• 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:
  317
• Issue:
  1
• NIOSHTIC Number:
  nn:20059056
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2019 Jul; 317(1):L127-L140
• Contact Point Address:
  V. Boggaram, Dept. of Cellular and Molecular Biology, Univ. of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154
• Email:
  vijay.boggaram@uthct.edu
• Federal Fiscal Year:
  2019
• 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:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:547fcda26f372dcbadef4be35df12bdda5e29f4a64b0c3e67dd8c48d17f4f24857b88c8567c97e8fb6ee4b5c0e288d2c6e02f966af94fd3b322c3d3210409402
• Download URL:
  https://stacks.cdc.gov/view/cdc/223382/cdc_223382_DS1.pdf
• File Type:
  [PDF - 2.61 MB ]