HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages
Hypoxia-inducible factor (HIF) 1α is a metabolic regulator that plays an important role in immunologic responses. Previous studies have demonstrated that HIF1α participates in the M1 polarization of macrophages. To clarify the mechanism of HIF1α-induced polarization of M1 macrophage, myeloid-specifi...
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Format: | Article |
Language: | English |
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Wiley
2017-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2017/9029327 |
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author | Ting Wang Huiying Liu Guan Lian Song-Yang Zhang Xian Wang Changtao Jiang |
author_facet | Ting Wang Huiying Liu Guan Lian Song-Yang Zhang Xian Wang Changtao Jiang |
author_sort | Ting Wang |
collection | DOAJ |
description | Hypoxia-inducible factor (HIF) 1α is a metabolic regulator that plays an important role in immunologic responses. Previous studies have demonstrated that HIF1α participates in the M1 polarization of macrophages. To clarify the mechanism of HIF1α-induced polarization of M1 macrophage, myeloid-specific HIF1α overexpression (Lysm HIF1α lsl) mice were employed and the bone marrow-derived and peritoneal macrophages were isolated. RT-PCR results revealed that HIF1α overexpression macrophage had a hyperinflammatory state characterized by the upregulation of M1 markers. Cellular bioenergetics analysis showed lower cellular oxygen consumption rates in the Lysm HIF1α lsl mice. Metabolomics studies showed that HIF1α overexpression led to increased glycolysis and pentose phosphate pathway intermediates. Further results revealed that macrophage M1 polarization, induced by HIF1α overexpression, was via upregulating the mRNA expression of the genes related to the glycolysis metabolism. Our results indicate that HIF1α promoted macrophage glycolysis metabolism, which induced M1 polarization in mice. |
format | Article |
id | doaj-art-a36f537ffb1d492e946f3d40ae3302f1 |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2017-01-01 |
publisher | Wiley |
record_format | Article |
series | Mediators of Inflammation |
spelling | doaj-art-a36f537ffb1d492e946f3d40ae3302f12025-02-03T05:58:44ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/90293279029327HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory MacrophagesTing Wang0Huiying Liu1Guan Lian2Song-Yang Zhang3Xian Wang4Changtao Jiang5Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaHypoxia-inducible factor (HIF) 1α is a metabolic regulator that plays an important role in immunologic responses. Previous studies have demonstrated that HIF1α participates in the M1 polarization of macrophages. To clarify the mechanism of HIF1α-induced polarization of M1 macrophage, myeloid-specific HIF1α overexpression (Lysm HIF1α lsl) mice were employed and the bone marrow-derived and peritoneal macrophages were isolated. RT-PCR results revealed that HIF1α overexpression macrophage had a hyperinflammatory state characterized by the upregulation of M1 markers. Cellular bioenergetics analysis showed lower cellular oxygen consumption rates in the Lysm HIF1α lsl mice. Metabolomics studies showed that HIF1α overexpression led to increased glycolysis and pentose phosphate pathway intermediates. Further results revealed that macrophage M1 polarization, induced by HIF1α overexpression, was via upregulating the mRNA expression of the genes related to the glycolysis metabolism. Our results indicate that HIF1α promoted macrophage glycolysis metabolism, which induced M1 polarization in mice.http://dx.doi.org/10.1155/2017/9029327 |
spellingShingle | Ting Wang Huiying Liu Guan Lian Song-Yang Zhang Xian Wang Changtao Jiang HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages Mediators of Inflammation |
title | HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages |
title_full | HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages |
title_fullStr | HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages |
title_full_unstemmed | HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages |
title_short | HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages |
title_sort | hif1α induced glycolysis metabolism is essential to the activation of inflammatory macrophages |
url | http://dx.doi.org/10.1155/2017/9029327 |
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