Activation of the JNK/COX-2/HIF-1α axis promotes M1 macrophage via glycolytic shift in HIV-1 infection
© 2023 Zhang et al..
Chronic inflammation is recognized as a major risk factor for the severity of HIV infection. Whether metabolism reprogramming of macrophages caused by HIV-1 is related to chronic inflammatory activation, especially M1 polarization of macrophages, is inconclusive. Here, we show that HIV-1 infection induces M1 polarization and enhanced glycolysis in macrophages. Blockade of glycolysis inhibits M1 polarization of macrophages, indicating that HIV-1-induced M1 polarization is supported by enhanced glycolysis. Moreover, we find that this immunometabolic adaptation is dependent on hypoxia-inducible factor 1α (HIF-1α), a strong inducer of glycolysis. HIF-1α-target genes, including HK2, PDK1, and LDHA, are also involved in this process. Further research discovers that COX-2 regulates HIF-1α-dependent glycolysis. However, the elevated expression of COX-2, enhanced glycolysis, and M1 polarization of macrophages could be reversed by inactivation of JNK in the context of HIV-1 infection. Our study mechanistically elucidates that the JNK/COX-2/HIF-1α axis is activated to strengthen glycolysis, thereby promoting M1 polarization in macrophages in HIV-1 infection, providing a new idea for resolving chronic inflammation in clinical AIDS patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Life science alliance - 6(2023), 12 vom: 05. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Junhan [VerfasserIn] |
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| Links: |
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| Themen: |
Cyclooxygenase 2 |
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| Anmerkungen: |
Date Completed 09.10.2023 Date Revised 18.10.2023 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.26508/lsa.202302148 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362917558 |
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| 245 | 1 | 0 | |a Activation of the JNK/COX-2/HIF-1α axis promotes M1 macrophage via glycolytic shift in HIV-1 infection |
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| 520 | |a © 2023 Zhang et al. | ||
| 520 | |a Chronic inflammation is recognized as a major risk factor for the severity of HIV infection. Whether metabolism reprogramming of macrophages caused by HIV-1 is related to chronic inflammatory activation, especially M1 polarization of macrophages, is inconclusive. Here, we show that HIV-1 infection induces M1 polarization and enhanced glycolysis in macrophages. Blockade of glycolysis inhibits M1 polarization of macrophages, indicating that HIV-1-induced M1 polarization is supported by enhanced glycolysis. Moreover, we find that this immunometabolic adaptation is dependent on hypoxia-inducible factor 1α (HIF-1α), a strong inducer of glycolysis. HIF-1α-target genes, including HK2, PDK1, and LDHA, are also involved in this process. Further research discovers that COX-2 regulates HIF-1α-dependent glycolysis. However, the elevated expression of COX-2, enhanced glycolysis, and M1 polarization of macrophages could be reversed by inactivation of JNK in the context of HIV-1 infection. Our study mechanistically elucidates that the JNK/COX-2/HIF-1α axis is activated to strengthen glycolysis, thereby promoting M1 polarization in macrophages in HIV-1 infection, providing a new idea for resolving chronic inflammation in clinical AIDS patients | ||
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| 700 | 1 | |a Yuan, Zongxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xuanrong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fengyi |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xueqin |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Yiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Mo, Chuye |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Junjun |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Li |e verfasserin |4 aut | |
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