NIOSHTIC-2 Publications Search
Protein kinase C epsilon is important in modulating organic-dust-induced airway inflammation.
Poole-JA; Romberger-DJ; Bauer-C; Gleason-AM; Sisson-JH; Oldenburg-PJ; West-WW; Wyatt-TA
Exp Lung Res 2012 Oct; 38(8):383-395
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.
Respiratory-hypersensitivity; Pulmonary-clearance; Lung-disorders; Lung-function; Airway-obstruction; Hypersensitivity; Immune-reaction; Organic-dusts; Dust-exposure; Dust-particles; Neutrophils; Oxides; Proteins; Sampling; Lung-cells; Lung-irritants; Cytotoxic-effects; In-vivo-study; Inhalation-studies; Laboratory-animals; Laboratory-testing; Biological-effects; Physiological-effects; Alveolar-cells; Lymphocytes; Methacholines; Nitrates; Nitrogen-oxides; Author Keywords: airway hyper-responsiveness; airway inflammation; lung; neutrophil; nitric oxide; protein kinase C epsilon
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
Cooperative Agreement; Grant
Issue of Publication
Agriculture, Forestry and Fishing
Experimental Lung Research
University of Nebraska Medical Center - Omaha
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division