2016 Progress Report: Airway Epithelium Organotypic Culture as a Platform for AdverseOutcomesPathway Assessment of Engineered Nanomaterials

EPA Grant Number: R835738C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R835738
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials
Center Director: Faustman, Elaine
Title: Airway Epithelium Organotypic Culture as a Platform for AdverseOutcomesPathway Assessment of Engineered Nanomaterials
Investigators: Altemeier, William
Institution: University of Washington
EPA Project Officer: Klieforth, Barbara I
Project Period: December 1, 2014 through November 30, 2018 (Extended to November 30, 2019)
Project Period Covered by this Report: December 1, 2015 through November 30,2016
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text |  Recipients Lists
Research Category: Safer Chemicals , Health , Human Health

Objective:

The overall goal of this project is to utilize mouse lung organotypic culture systems to better evaluate for cellular and organ toxicity to relevant engineered nanoparticles. The lungs are a major route of exposure to environmental and occupational compounds, and the airway epithelium is the primary surface for initial contact and management of inhaled exogenous materials. This project therefore focuses on using primary epithelial cells differentiated at an air-liquid system as the basis for modeling. This cell system represents an organotypic model system consisting of a combination of ciliated epithelium and club (Clara) secretory cells. Furthermore, altering the defined culture medium can skew the cell phenotype towards a mucus secretory cell type (aka goblet cells) to model chronic airway diseases. The culture system also can be combined with stromal cells in the basal chamber and/or macrophages in the apical chamber to further extend the relevance of the model system.

Progress Summary:

Our progress and findings include:

  • Co-culture of epithelial cells with macrophages does not enhance epithelial cell cytotoxicity in response to silver nanoparticles.
  • Cadmium:  Airway epithelial cells are more susceptible to cytotoxicity from cadmium as compared with silver nanomaterials.
  • Silver Nanoparticle:  Primary mouse airway epithelial cells differentiated with IL13 to model asthma are more susceptible to AgNP-induced cytotoxicity than normal airways.

 

Future Activities:

We have collected RNA and supernatants from a series of experiments in which IL13-differentiated alveolar epithelial cells were exposed to silver nanoparticles. These will be assessed for our inflammatory, oxidative stress, and differentiation assays this spring.

We will evaluate toxicity of cadmium in IL13 differentiated airway epithelial cell culture and contrast it with the response of normally differentiated airway epithelial cells.

We will assess biotoxicity of silver nanoparticles and cadmium in proliferating undifferentiated airway epithelial cells, which is our model system for impact on wounded epithelium.


Journal Articles on this Report : 1 Displayed | Download in RIS Format

Other subproject views: All 11 publications 3 publications in selected types All 3 journal articles
Other center views: All 134 publications 39 publications in selected types All 38 journal articles
Type Citation Sub Project Document Sources
Journal Article Cartwright MM, Schmuck SC, Corredor C, Wang B, Scoville DK, Chisholm CR, Wilkerson HW, Afsharinejad Z, Bammler TK, Posner JD, Shutthanandan V, Baer DR, Mitra S, Altemeier WA, Kavanagh TJ. The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis. Redox Biology 2016;9:264-275. R835738 (2016)
R835738 (2017)
R835738 (2018)
R835738C001 (2016)
  • Full-text from PubMed
  • Abstract from PubMed
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  • Supplemental Keywords:

    airway, lung, engineered nanomaterials

    Relevant Websites:

    The Predictive Toxicology Center (PTC) for Organotypic Cultures Exit

    Progress and Final Reports:

    Original Abstract
  • 2015 Progress Report
  • 2017 Progress Report
  • 2018

  • Main Center Abstract and Reports:

    R835738    Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R835738C001 Airway Epithelium Organotypic Culture as a Platform for AdverseOutcomesPathway Assessment of Engineered Nanomaterials
    R835738C002 Organotypic Model of Human Kidney as a Platform for Adverse Outcomes Pathway Assessment of Engineered Nanomaterials
    R835738C003 Organotypic Models of Mammalian Liver as a Platform for Adverse Outcomes Pathway Assessment of Engineered Nanomaterials
    R835738C004 Organotypic Model of Testis as a Platform for Adverse Outcomes Pathway Assessment of Engineered Nanomaterials
    R835738C005 Integrating Liver, Kidney and Testis Nanomaterial Toxicity using the Adverse Outcome Pathway Approach