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Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells



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  • Personal Author:
  • Description:
    Background: Persistant inflammatory responses to infectious agents and other components in organic dust underlie lung injury and development of respiratory diseases. Organic dust components responsible for eliciting inflammation and the mechanisms by which they cause lung inflammation are not fully understood. We studied the mechanisms by which protease activities in poultry dust extracts and intracellular oxidant stress induce inflammatory gene expression in A549 and Beas2B lung epithelial cells. Methods: The effects of dust extracts on inflammatory gene expression were analyzed by quantitative polymerase chain reaction (qPCR), enzyme linked immunosorbent (ELISA) and western blot assays. Oxidant stress was probed by dihydroethidium (DHE) labeling, and immunostaining for 4-hydroxynonenal (4-HNE). Effects on interleukin-8 (IL-8) promoter regulation were determined by transient transfection assay. Results: Dust extracts contained trypsin and elastase activities, and activated protease activated receptor (PAR)-1 and -2. Serine protease inhibitors and PAR-1 or PAR-2 knockdown suppressed inflammatory gene induction. Dust extract induction of IL-8 gene expression was associated with increased DHE-fluorescence and 4-HNE staining, and antioxidants suppressed inflammatory gene induction. Protease inhibitors and antioxidants suppressed protein kinase C and NF-kappaB activation and induction of IL-8 promoter activity in cells exposed to dust extract. Conclusions: Our studies demonstrate that proteases and intracellular oxidants control organic dust induction of inflammatory gene expression in lung epithelial cells. Targeting proteases and oxidant stress may serve as novel approaches for the treatment of organic dust induced lung diseases. This is the first report on the involvement of oxidant stress in the induction of inflammatory gene expression by organic dust. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    1465-9921
  • Document Type:
    Text
  • Funding:
    Cooperative Agreement
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Volume:
    17
  • NIOSHTIC Number:
    nn:20049372
  • Citation:
    Respir Res 2016 Oct; 17:137
  • Contact Point Address:
    V. Boggaram, Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA
  • Email:
    vijay.boggaram@uthct.edu
  • Federal Fiscal Year:
    2017
  • 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:
    Respiratory Research
  • End Date:
    20270929
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:888d71628701757f3c3a2c20071d06251448d5705d37e9ab9155d7e2f93976ea6db3bb42b2c83d220e88b872ee10a607f032317970785f2bba6a49576258df49
  • Download URL:
  • File Type:
    Filetype[PDF - 2.79 MB ]
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