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TREM-1 governs NLRP3 inflammasome activation of macrophages by firing up glycolysis in acute lung injury.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2023 Jan 01; Vol. 19 (1), pp. 242-257. Date of Electronic Publication: 2023 Jan 01 (Print Publication: 2023). - Publication Year :
- 2023
-
Abstract
- The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory immune receptor potentiating acute lung injury (ALI). However, the mechanism of TREM-1-triggered inflammation response remains poorly understood. Here, we showed that TREM-1 blocking attenuated NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome activation and glycolysis in LPS-induced ALI mice. Then, we observed that TREM-1 activation enhanced glucose consumption, induced glycolysis, and inhibited oxidative phosphorylation in macrophages. Specifically, inhibition of glycolysis with 2-deoxyglucose diminished NLRP3 inflammasome activation of macrophages triggered by TREM-1. Hypoxia-inducible factor-1α (HIF-1α) is a critical transcriptional regulator of glycolysis. We further found that TREM-1 activation facilitated HIF-1α accumulation and translocation to the nucleus via the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Inhibiting mTOR or HIF-1α also suppressed TREM-1-induced metabolic reprogramming and NLRP3/caspase-1 activation. Overall, the mTOR/HIF-1α/glycolysis pathway is a novel mechanism underlying TREM-1-governed NLRP3 inflammasome activation. Therapeutic targeting of the mTOR/HIF-1α/glycolysis pathway in TREM-1-activated macrophages could be beneficial for treating or preventing inflammatory diseases, such as ALI.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Mice
Triggering Receptor Expressed on Myeloid Cells-1 metabolism
NLR Family, Pyrin Domain-Containing 3 Protein genetics
Phosphatidylinositol 3-Kinases metabolism
Mice, Inbred NOD
Macrophages metabolism
TOR Serine-Threonine Kinases metabolism
Glycolysis
Lipopolysaccharides
Mice, Inbred C57BL
Mammals metabolism
Inflammasomes metabolism
Acute Lung Injury chemically induced
Acute Lung Injury metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36594089
- Full Text :
- https://doi.org/10.7150/ijbs.77304