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


ABSTRACT: 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, PKC?. PKC? is also rapidly activated in murine tracheal epithelial cells following in vivo organic dust challenges, yet the functional role of PKC? 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 PKC? knock-out (KO) mice. We found that neutrophil influx increased more than twofold in PKC? 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 PKC? KO mice. Airway hyperresponsiveness to methacholine increased in PKC? 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 PKC? KO mice. Moreover, ODE failed to upregulate NO from ex vivo stimulated PKC? KO lung macrophages. Collectively, these studies demonstrate that PKC?-deficient mice were hypersensitive to organic dust exposure and suggest that PKC? is important in the normative lung inflammatory response to ODE. Dampening of ODE-induced NO may contribute to these enhanced inflammatory findings.

SUBMITTER: Poole JA 

PROVIDER: S-EPMC4066446 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Poole Jill A JA   Romberger Debra J DJ   Bauer Chris C   Gleason Angela M AM   Sisson Joseph H JH   Oldenburg Peter J PJ   West William W WW   Wyatt Todd A TA  

Experimental lung research 20120816 8


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, PKCε. PKCε is also rapidly activated in murine tracheal epithelial cells following in vivo organic dust challenges, yet the functional role of PKCε in modulating dust-induced airway inflammatory outcomes is not defined. Utilizing an established intranasal inh  ...[more]

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