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HIF-1α regulates IL-1β and IL-17 in sarcoidosis.
- Source :
-
ELife [Elife] 2019 May 01; Vol. 8. Date of Electronic Publication: 2019 May 01. - Publication Year :
- 2019
-
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 <superscript>+</superscript> 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.<br />Competing Interests: JT, HT, CB, LG, KZ, PT, LS No competing interests declared<br /> (© 2019, Talreja et al.)
- Subjects :
- Adolescent
Adult
Female
Humans
Inflammation pathology
Lung pathology
Macrophages pathology
Male
Monocytes pathology
Th1 Cells immunology
Th17 Cells immunology
Young Adult
Gene Expression Regulation
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Interleukin-17 biosynthesis
Interleukin-1beta biosynthesis
Sarcoidosis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 30946009
- Full Text :
- https://doi.org/10.7554/eLife.44519