Protein kinase C epsilon is important in modulating organic-dust-induced airway inflammation

Details

• Personal Author:
  Bauer C ; Gleason AM ; Oldenburg PJ ; Poole JA ; Romberger DJ ; Sisson JH ; West WW ; Wyatt TA
• Description:
  Organic dust samples from swine confinement facilities elicit pro-inflammatory cytokine/chemokine release from bronchial epithelial cells and monocytes, dependent, in part, upon dust-induced activation of the protein kinase C (PKC) isoform, PKCe. PKCe is also rapidly activated in murine tracheal epithelial cells following in vivo organic dust challenges, yet the functional role of PKCe in modulating dust-induced airway inflammatory outcomes is not defined. Utilizing an established intranasal inhalation animal model, experiments investigated the biologic and physiologic responses following organic dust extract (ODE) treatments in wild-type (WT) and PKCe knock-out (KO) mice. We found that neutrophil influx increased more than twofold in PKCe KO mice following both a one-time challenge and 3 weeks of daily challenges with ODE as compared with WT mice. Lung pathology revealed increased bronchiolar and alveolar inflammation, lymphoid aggregates, and T cell influx in ODE-treated PKCe KO mice. Airway hyperresponsiveness to methacholine increased in PKCe KO + ODE to a greater magnitude than WT + ODE animals. There were no significant differences in cytokine/chemokine release elicited by ODE treatment between groups. However, ODE-induced nitric oxide (NO) production differed in that ODE exposure increased nitrate levels in WT mice but not in PKCe KO mice. Moreover, ODE failed to upregulate NO from ex vivo stimulated PKCe KO lung macrophages. Collectively, these studies demonstrate that PKCe-deficient mice were hypersensitive to organic dust exposure and suggest that PKCe is important in the normative lung inflammatory response to ODE. Dampening of ODE-induced NO may contribute to these enhanced inflammatory findings. [Description provided by NIOSH]
• Subjects:
  Blood Cytotoxins Dust Immune System Laboratories Lung Methacholine Compounds Nitrates Nitrogen Oxides Occupational Health Respiratory Hypersensitivity Respiratory System Safety

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• Keywords:
  Airway-obstruction Airway Inflammation Alveolar-cells Author Keywords: Airway Hyper-responsiveness Cytotoxic-effects Dust-exposure Dust-particles Immune-reaction In-vivo-study Inhalation-studies Laboratory-animals Lung Lung-irritants Lymphocytes Methacholines Neutrophil Neutrophils Nitric Oxide Nitrogen-oxides Organic-dusts Protein Kinase C Epsilon Proteins Respiratory-hypersensitivity

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• ISSN:
  0190-2148
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• 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:
  383-395
• Volume:
  38
• Issue:
  8
• NIOSHTIC Number:
  nn:20042195
• Citation:
  Exp Lung Res 2012 Oct; 38(8):383-395
• Contact Point Address:
  Jill A. Poole, Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300, USA
• Email:
  japoole@unmc.edu
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Experimental Lung Research
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:52e01134f11bcd6f20ed4f78a504bc5e14ecb6a7e5591e2ce440640219a54f8696c8aa52485d0d36249fdc62bc00596f883148d19efa607ff2c6ab4d198dd01f
• Download URL:
  https://stacks.cdc.gov/view/cdc/194495/cdc_194495_DS1.pdf
• File Type:
  [PDF - 1.37 MB ]