Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 110, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.109049
Keywords
Acute lung injury; Phloretin; GLUT1; Glycolysis; Macrophage
Categories
Funding
- Fundamental Research Funds for the Central Universities [2042021kf0100, 2042021kf0127]
- Hubei Provincial central guiding local science and technology development special project [2019ZYYD065]
- Enterprise Cooperation Project [2021HX0003]
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This study found that phloretin (PHL), an apple polyphenol, can prevent lipopolysaccharide (LPS)-induced acute lung injury (ALI) by inhibiting glycolysis in macrophages, and its action depends on the inhibition of glucose transporter 1 (GLUT1).
The increased level of glycolysis in macrophage aggravates lipopolysaccharide (LPS)-induced acute lung injury (ALI). Glucose transporter 1 (GLUT1) serves as a ubiquitously expressed glucose transporter, which could acti-vate inflammatory response by mediating glycolysis. Phloretin (PHL), an apple polyphenol, is also an inhibitor of GLUT1, possessing potent anti-inflammatory effects in various diseases. However, the potential role of PHL in ALI remains unclear till now. This study aims to investigate the impacts of PHL on ALI as well as its possible mechanisms. A mouse ALI model was established via intratracheal injection of LPS. LPS-induced primary macrophages were used to mimic in vitro ALI. Mice were pretreated with low or high dosage of PHL for 7 days via intragastric administration once a day before LPS injection. The results showed that PHL pretreatment significantly prevented LPS-induced lung pathological injury and inflammatory response. Meantime, PHL pre-treatment also decreased the level of glycolysis in macrophage during ALI. In terms of mechanism, PHL inhibited the mRNA and protein expression of GLUT1. In vitro experiments further showed GLUT1 overexpression in macrophage by infection with lentivirus could abolish the inhibition of inflammation and glycolysis mediated by PHL, suggesting that GLUT1 was essential for the protection of PHL. Taken together, PHL pretreatment may protect against LPS-induced ALI by inhibiting glycolysis in macrophage in a GLUT1-dependent manner, which may be a candidate against ALI in the future.
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