Bidirectional regulation of bronchial epithelial function by PKA and PKC in organic dust-induced airway injury.
Wyatt-TA; Sisson-JH; DeVasure-J; Yanov-D; Heires-A; Romberger-DJ
Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A4671
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.
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
Agriculture, Forestry and Fishing
American Journal of Respiratory and Critical Care Medicine
University of Nebraska Medical Center, Omaha, Nebraska