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- W2932199720 abstract "Sarcoidosis is a complex systemic granulomatous disease of unknown etiology characterized by the presence of activated macrophages and Th1/Th17 effector cells. Data mining of our RNA-Seq analysis of CD14 + monocytes showed enrichment for metabolic and hypoxia inducible factor (HIF) pathways in sarcoidosis. Further investigation revealed that sarcoidosis macrophages and monocytes exhibit higher protein levels for HIF-α isoforms, HIF-1β, and their transcriptional co-activator p300 as well as glucose transporter 1 (Glut1). In situ hybridization of sarcoidosis granulomatous lung tissues showed abundance of HIF-1α in the center of granulomas. The abundance of HIF isoforms was mechanistically linked to elevated IL-1β and IL-17 since targeted down regulation of HIF-1α via short interfering RNA or a HIF-1α inhibitor decreased their production. Pharmacological intervention using chloroquine, a lysosomal inhibitor, decreased lysosomal associated protein 2 (LAMP2) and HIF-1α levels and modified cytokine production. These data suggest that increased activity of HIF-α isoforms regulate Th1/Th17 mediated inflammation in sarcoidosis." @default.
- W2932199720 created "2019-04-11" @default.
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- W2932199720 date "2019-05-01" @default.
- W2932199720 modified "2023-10-04" @default.
- W2932199720 title "HIF-1α regulates IL-1β and IL-17 in sarcoidosis" @default.
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- W2932199720 doi "https://doi.org/10.7554/elife.44519" @default.
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