Factors influencing vitamin a secretion in macrophages
Sim, Jaeyoung
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Permalink
https://hdl.handle.net/2142/122072
Description
Title
Factors influencing vitamin a secretion in macrophages
Author(s)
Sim, Jaeyoung
Issue Date
2023-12-08
Director of Research (if dissertation) or Advisor (if thesis)
Amengual, Jaume
Department of Study
Food Science & Human Nutrition
Discipline
Food Science & Human Nutrition
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
Vitamin A, Macrophages
Abstract
Vitamin A plays a crucial role in modulating macrophage function. Our group recently showed that retinoic acid, the transcriptionally active form of vitamin A, is released by cultured macrophages, which could influence the differentiation of other cell types such as T-cells. The objective of this study is to elucidate the mechanisms that regulate vitamin A secretion from macrophages. Using a method developed in our lab that allows us to load cells with vitamin A, we compared the release of retinoids (retinol and retinyl esters) between macrophages and hepatocytes by performing kinetic studies. Next, we focused on the mechanisms that regulate vitamin A secretion in the macrophage. We measured intracellular (cell lysates) and extracellular (media) retinoids by high-performance liquid chromatography. To examine the mechanisms implicated in vitamin A release, cells were exposed to different experimental conditions such as chloroquine to block lysosomal degradation and GW4869 to block exosome formation. We also utilized the macrophages isolated from apolipoprotein E and retinol-binding protein 4 deficient mice to test the role of these transporters on vitamin A release in macrophages. Blocking lysosomal activity led to an increase in intracellular retinyl ester levels without affecting retinoid secretion. The inhibition of exosome formation reduced retinoid secretion from macrophages, and vitamin A was present in purified exosomes, suggesting that the exosomal pathway contributes to vitamin A secretion from the macrophage.
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