NIOSHTIC-2 Publications Search

Bidirectional regulation of bronchial epithelial function by PKA and PKC in organic dust-induced airway injury.

Authors
Wyatt-TA; Sisson-JH; DeVasure-J; Yanov-D; Heires-A; Romberger-DJ
Source
Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A4671
NIOSHTIC No.
20037185
Abstract
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.
Keywords
Airborne-particles; Airway-obstruction; Biological-effects; Biological-monitoring; Cell-function; Cell-metabolism; Cell-transformation; Cellular-function; Cellular-reactions; Cytology; Cytotoxic-effects; Dust-exposure; Dust-measurement; Dust-particles; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-testing; Lung; 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
CODEN
AJCMED
Publication Date
20100501
Document Type
Abstract
Email Address
lrichard@unmc.edu
Funding Type
Grant
Fiscal Year
2010
Identifying No.
Grant-Number-R01-OH-008539
ISSN
1073-449X
Priority Area
Agriculture, Forestry and Fishing
Source Name
American Journal of Respiratory and Critical Care Medicine
State
NE
Performing Organization
University of Nebraska Medical Center, Omaha, Nebraska
Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division