Bidirectional Regulation of Bronchial Epithelial Function by PKA and PKC in Organic Dust-Induced Airway Injury

Details

• Personal Author:
  DeVasure J ; Heires A ; Romberger DJ ; Sisson JH ; Wyatt TA ; Yanov D
• Description:
  Bidirectional regulation of signal transduction by protein kinase C (PKC) and the cAMP-dependent protein kinase (PKA) have been observed in neuronal and inflammatory cells. Bronchial epithelial cell functions such as cilia beating and wound repair are enhanced by PKA-activating agents and diminished by PKC-activating agents. Previously, we have shown that organic dusts from confined animal feeding operations stimulate airway epithelial cell proinflammatory cytokine release via a PKC-dependent manner. We hypothesized that a mechanism of bidirectional regulation of airway epithelial function exists that is driven by the net balance of PKA/PKC activity. Primary bovine bronchial epithelial cells were grown in culture and assayed for PKA and PKC activity using a direct specific substrate radiolabeled-phosphate incorporation assay. Kinase activities were compared to measurements of organic dust-stimulated increases in interleukin-8 release. We observed that pretreating bronchial epithelial cells with beta agonists, forskolin, or cell-permeable cAMP analogs blocked organic dust-induced PKC epsilon activation. Likewise, alcohol pretreatment under conditions of cAMP elevation and PKA activation resulted in the inhibition of organic dust-stimulated PKC epsilon activity. Organic dust-induced release of interleukin-8, a process dependent upon PKC activation, was significantly diminished in response to PKA activating agents. These data provide evidence for PKA as a negative regulator to PKC-driven signaling inflammatory events in airway epithelium and suggests that PKA plays an anti-inflammatory role in the lung. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Cytology Cytotoxins Dust Environmental Monitoring Hazardous Substances Irritants Laboratories Lung Lung Diseases Microbiology Occupational Diseases Occupational Exposure Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Risk Assessment Safety Workplace

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• Keywords:
  Airborne-particles Airway-obstruction Biological-effects Biological-monitoring Cell-function Cell-metabolism Cell-transformation Cellular-function Cellular-reactions Cytotoxic-effects Dust-exposure Dust-measurement Dust-particles Exposure-assessment Exposure-levels Exposure-methods Inhalation-studies Laboratory-testing Lung-burden Lung-cells Lung-disease Lung-disorders Lung-function Lung-irritants Microscopic-analysis Occupational-diseases Occupational-exposure Occupational-hazards Occupational-health Occupational-respiratory-disease Organic-dusts Particle-aerodynamics Particulate-dust Particulates Pulmonary-congestion Pulmonary-disorders Pulmonary-function Pulmonary-system Pulmonary-system-disorders Quantitative-analysis Respirable-dust Respiratory-hypersensitivity Respiratory-infections Respiratory-irritants Respiratory-system-disorders Risk-analysis Statistical-analysis Toxic-effects Work-areas Work-environment Work-operations Work-performance Workplace-monitoring Workplace-studies

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• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  181
• NIOSHTIC Number:
  nn:20037185
• Citation:
  Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A4671
• Email:
  lrichard@unmc.edu
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  False
• Start Date:
  20060801
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Meeting Abstracts
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:141ba13de858a07a16b03b69ae18098db3bd0751c9e2e8d12ec94bda343292d12b501bbff79da6395fbd04099fda5990e844893b162104185b94572a23b8dfb9
• Download URL:
  https://stacks.cdc.gov/view/cdc/188317/cdc_188317_DS1.pdf
• File Type:
  [PDF - 16.71 KB ]