Bovine milk-derived extracellular vesicles enhance inflammation and promote M1 polarization following agricultural dust exposure in mice

Research output: Contribution to journalArticle

Abstract

Occupational agricultural dust exposure can cause severe lung injury, including COPD and asthma exacerbations. Cell-derived extracellular vesicles can mediate inflammatory responses and immune activation, but the contribution of diet-derived extracellular vesicles to these processes is poorly understood. We investigated whether bovine milk-derived extracellular vesicles modulate inflammatory responses to agricultural dust exposures in a murine model. C57BL/6 mice were fed either an extracellular vesicle-enriched modification of the AIN-93G diet with lyophilized bovine milk (EV) or a control diet wherein the milk was presonicated, disrupting the milk extracellular vesicles and thereby leading to RNA degradation (DEV). Mice were maintained on the diets for 5–7 weeks and challenged with a single (acute) intranasal instillation of a 12.5% organic dust extract (DE) or with 15 instillations over 3 weeks (repetitive exposure model). Through these investigations, we identified significant interactions between diet and DE when considering numerous inflammatory outcomes, including lavage inflammatory cytokine levels and cellular infiltration into the lung airways. DE-treated peritoneal macrophages also demonstrated altered polarization, with EV-fed mouse macrophages exhibiting an M1 shift compared to an M2 phenotype in DEV-fed mice (IL-6, TNF, IL-12/23 all significantly elevated, and IL-10 and arginase decreased in EV macrophages, ex vivo). In complementary in vitro studies, mouse macrophages treated with purified milk-derived EV were found to express similar polarization phenotypes upon DE stimulation. These results suggest a role for dietary extracellular vesicles in the modulation of lung inflammation in response to organic dust which may involve macrophage phenotype polarization.

LanguageEnglish (US)
Pages110-120
Number of pages11
JournalJournal of Nutritional Biochemistry
Volume64
DOIs
StatePublished - Feb 1 2019

Fingerprint

Dust
Macrophages
Milk
Nutrition
Polarization
Inflammation
Diet
Phenotype
Interleukin-23
Arginase
Therapeutic Irrigation
RNA Stability
Peritoneal Macrophages
Lung Injury
Interleukin-12
Extracellular Vesicles
Inbred C57BL Mouse
Infiltration
Interleukin-10
Chronic Obstructive Pulmonary Disease

Keywords

  • Agriculture exposures
  • Lung inflammation
  • Macrophages
  • Milk extracellular vesicles
  • Organic dust

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

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title = "Bovine milk-derived extracellular vesicles enhance inflammation and promote M1 polarization following agricultural dust exposure in mice",
abstract = "Occupational agricultural dust exposure can cause severe lung injury, including COPD and asthma exacerbations. Cell-derived extracellular vesicles can mediate inflammatory responses and immune activation, but the contribution of diet-derived extracellular vesicles to these processes is poorly understood. We investigated whether bovine milk-derived extracellular vesicles modulate inflammatory responses to agricultural dust exposures in a murine model. C57BL/6 mice were fed either an extracellular vesicle-enriched modification of the AIN-93G diet with lyophilized bovine milk (EV) or a control diet wherein the milk was presonicated, disrupting the milk extracellular vesicles and thereby leading to RNA degradation (DEV). Mice were maintained on the diets for 5–7 weeks and challenged with a single (acute) intranasal instillation of a 12.5{\%} organic dust extract (DE) or with 15 instillations over 3 weeks (repetitive exposure model). Through these investigations, we identified significant interactions between diet and DE when considering numerous inflammatory outcomes, including lavage inflammatory cytokine levels and cellular infiltration into the lung airways. DE-treated peritoneal macrophages also demonstrated altered polarization, with EV-fed mouse macrophages exhibiting an M1 shift compared to an M2 phenotype in DEV-fed mice (IL-6, TNF, IL-12/23 all significantly elevated, and IL-10 and arginase decreased in EV macrophages, ex vivo). In complementary in vitro studies, mouse macrophages treated with purified milk-derived EV were found to express similar polarization phenotypes upon DE stimulation. These results suggest a role for dietary extracellular vesicles in the modulation of lung inflammation in response to organic dust which may involve macrophage phenotype polarization.",
keywords = "Agriculture exposures, Lung inflammation, Macrophages, Milk extracellular vesicles, Organic dust",
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AU - Nordgren, Tara M.

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AU - Zempleni, Janos

AU - Swanson, Benjamin J

AU - Wichman, Christopher S

AU - Romberger, Debra

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