HIF-1α regulates IL-1β and IL-17 in sarcoidosis
Identifieur interne : 004017 ( Main/Exploration ); précédent : 004016; suivant : 004018HIF-1α regulates IL-1β and IL-17 in sarcoidosis
Auteurs : Jaya Talreja [États-Unis] ; Harvinder Talwar [États-Unis] ; Christian Bauerfeld [États-Unis] ; Lawrence I. Grossman [États-Unis] ; Kezhong Zhang [États-Unis] ; Paul Tranchida [États-Unis] ; Lobelia Samavati [États-Unis]Source :
- eLife [ 2050-084X ] ; ????.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Cellules Th17 (immunologie), Femelle, Humains, Inflammation (anatomopathologie), Interleukine-1 bêta (biosynthèse), Interleukine-17 (biosynthèse), Jeune adulte, Lymphocytes auxiliaires Th1 (immunologie), Macrophages (anatomopathologie), Monocytes (anatomopathologie), Mâle, Poumon (anatomopathologie), Régulation de l'expression des gènes, Sarcoïdose (anatomopathologie), Sous-unité alpha du facteur-1 induit par l'hypoxie (métabolisme).
- MESH :
- anatomopathologie : Inflammation, Macrophages, Monocytes, Poumon, Sarcoïdose.
- biosynthèse : Interleukine-1 bêta, Interleukine-17.
- immunologie : Cellules Th17, Lymphocytes auxiliaires Th1.
- métabolisme : Sous-unité alpha du facteur-1 induit par l'hypoxie.
- Adolescent, Adulte, Femelle, Humains, Jeune adulte, Mâle, Régulation de l'expression des gènes.
English descriptors
- KwdEn :
- Adolescent, Adult, Female, Gene Expression Regulation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit (metabolism), Inflammation (pathology), Interleukin-17 (biosynthesis), Interleukin-1beta (biosynthesis), Lung (pathology), Macrophages (pathology), Male, Monocytes (pathology), Sarcoidosis (pathology), Th1 Cells (immunology), Th17 Cells (immunology), Young Adult.
- MESH :
- chemical , biosynthesis : Interleukin-17, Interleukin-1beta.
- chemical , metabolism : Hypoxia-Inducible Factor 1, alpha Subunit.
- immunology : Th1 Cells, Th17 Cells.
- pathology : Inflammation, Lung, Macrophages, Monocytes, Sarcoidosis.
- Adolescent, Adult, Female, Gene Expression Regulation, Humans, Male, Young Adult.
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.
Url:
DOI: 10.7554/eLife.44519
PubMed: 30946009
PubMed Central: 6506207
Affiliations:
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Le document en format XML
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xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Cellules Th17 (immunologie)</term><term>Femelle</term><term>Humains</term><term>Inflammation (anatomopathologie)</term><term>Interleukine-1 bêta (biosynthèse)</term><term>Interleukine-17 (biosynthèse)</term><term>Jeune adulte</term><term>Lymphocytes auxiliaires Th1 (immunologie)</term><term>Macrophages (anatomopathologie)</term><term>Monocytes (anatomopathologie)</term><term>Mâle</term><term>Poumon (anatomopathologie)</term><term>Régulation de l'expression des gènes</term><term>Sarcoïdose (anatomopathologie)</term><term>Sous-unité alpha du facteur-1 induit par l'hypoxie (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interleukin-17</term><term>Interleukin-1beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hypoxia-Inducible Factor 1, alpha Subunit</term></keywords><keywords scheme="MESH" 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Data mining of our RNA-Seq analysis of CD14<sup>+</sup>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aberdein, Jd" uniqKey="Aberdein J">JD Aberdein</name></author><author><name sortKey="Cole, J" uniqKey="Cole J">J Cole</name></author><author><name sortKey="Bewley, Ma" uniqKey="Bewley M">MA Bewley</name></author><author><name sortKey="Marriott, Hm" uniqKey="Marriott H">HM Marriott</name></author><author><name sortKey="Dockrell, Dh" uniqKey="Dockrell D">DH Dockrell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arend, Wp" uniqKey="Arend W">WP Arend</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Avril, N" uniqKey="Avril N">N Avril</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ben Haim, S" uniqKey="Ben Haim S">S Ben-Haim</name></author><author><name 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Grossman</name><name sortKey="Samavati, Lobelia" sort="Samavati, Lobelia" uniqKey="Samavati L" first="Lobelia" last="Samavati">Lobelia Samavati</name><name sortKey="Talwar, Harvinder" sort="Talwar, Harvinder" uniqKey="Talwar H" first="Harvinder" last="Talwar">Harvinder Talwar</name><name sortKey="Tranchida, Paul" sort="Tranchida, Paul" uniqKey="Tranchida P" first="Paul" last="Tranchida">Paul Tranchida</name><name sortKey="Zhang, Kezhong" sort="Zhang, Kezhong" uniqKey="Zhang K" first="Kezhong" last="Zhang">Kezhong Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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