Details:

Alternative Title:
Exp Lung Res
Publisher's site:
http://dx.doi.org/10.3109/01902148.2012.714841
Personal Author:
Poole, Jill A. ; Romberger, Debra J. ; Bauer, Chris ; Gleason, Angela M. ; Sisson, Joseph ; ... More +
Poole, Jill A. ; Romberger, Debra J. ; Bauer, Chris ; Gleason, Angela M. ; Sisson, Joseph ; Oldenburg, Peter J. ; West, William W. ; Wyatt, Todd A. Less -
Description:
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 inhalation animal model, experiments investigated the biologic and physiologic responses following organic dust extract (ODE) treatments in wild-type (WT) and PKCε knock-out (KO) mice. We found that neutrophil influx increased more than twofold in PKCε 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 PKCε KO mice. Airway hyperresponsiveness to methacholine increased in PKCε 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 PKCε KO mice. Moreover, ODE failed to upregulate NO from ex vivo stimulated PKCε KO lung macrophages. Collectively, these studies demonstrate that PKCε-deficient mice were hypersensitive to organic dust exposure and suggest that PKCε is important in the normative lung inflammatory response to ODE. Dampening of ODE-induced NO may contribute to these enhanced inflammatory findings.
Subject:
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Airway Hyper-responsiveness Airway Inflammation Animals Article Bronchial Hyperreactivity Bronchial Provocation Tests Chemokines Disease Models, Animal Dust Environmental Exposure Enzyme Activation Female Inflammation Mediators Lung Male Methacholine Chloride Mice Mice, Inbred C57BL Mice, Knockout Neutrophil Neutrophil Infiltration Nitric Oxide Protein Kinase C-epsilon Protein Kinase C Epsilon T-Lymphocytes Lung
Source:
Exp Lung Res. 38(8):383-395.
Pubmed ID:
22897707
Pubmed Central ID:
PMC4066446
Document Type:
Journal Article
Funding:
ES015522-03S1/ES/NIEHS NIH HHS/United States ; K08 ES015522/ES/NIEHS NIH HHS/United States ; K08 ES015522-01/ES/NIEHS NIH HHS/United States ; P01OH010162/OH/NIOSH CDC HHS/United States ; R01 AA008769/AA/NIAAA NIH HHS/United States ; ... More +
ES015522-03S1/ES/NIEHS NIH HHS/United States ; K08 ES015522/ES/NIEHS NIH HHS/United States ; K08 ES015522-01/ES/NIEHS NIH HHS/United States ; P01OH010162/OH/NIOSH CDC HHS/United States ; R01 AA008769/AA/NIAAA NIH HHS/United States ; R01 AA017993/AA/NIAAA NIH HHS/United States ; R01 ES019325/ES/NIEHS NIH HHS/United States ; R01 ES019325/ES/NIEHS NIH HHS/United States ; R01AA017993/AA/NIAAA NIH HHS/United States ; R01OH008539/OH/NIOSH CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:1f4ecc6a059c8055f8bc648889bee43d3519e64362ea951c745e292849c6674b
Download URL:
https://stacks.cdc.gov/view/cdc/33692/cdc_33692_DS1.pdf
File Type:

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