促炎细胞因子
慢性鼻-鼻窦炎
碳水化合物代谢
功能(生物学)
细胞代谢
内科学
新陈代谢
炎症
生物
医学
细胞生物学
作者
Cailing Chen,Jin Ma,Ruo-Yu Lu,Yuting Wang,Jiajia Zhao,Yi-Fan Kang,Jia Hu,Nan Wang,Jia Song,Jixin Zhong,Chen Chen,Heng Wang,Zheng Liu
标识
DOI:10.1016/j.jaci.2022.09.036
摘要
Glucose concentrations are increased in nasal secretions in chronic rhinosinusitis (CRS). However, the glucose metabolism and its contribution to disease pathogenesis in CRS remain unexplored.We sought to explore the glucose metabolism and its effect on the function of nasal epithelial cells in CRS with and without nasal polyps (CRSwNP and CRSsNP).Glucose metabolites were detected with mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were detected by quantitative RT-PCR. The protein expression of GLUTs was studied by immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was measured by using fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured. Bioenergetic analysis was performed with Seahorse XF analyzer. Gene expression in HNECs was profiled by RNA sequencing.Increased glucose concentrations in nasal secretions was confirmed in both CRSsNP and CRSwNP. GLUT4, GLUT10, and GLUT11 were abundantly expressed in HNECs, whose expression was upregulated by inflammatory cytokines and D-glucose and was increased in CRS. Glucose uptake, glycolysis and tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were increased in HNECs in CRSsNP and CRSwNP, with a predominant shift to glycolysis. HNECs treated with high-level apical D-glucose showed enhanced glucose uptake, predominant glycolysis, and upregulated production of IL-1α, IL-1β, TNF-α, CCL20, and CXCL8, which was suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis.Increased glucose in nasal secretions promotes glucose uptake and predominant glycolysis in epithelial cells, augmenting the proinflammatory function of epithelial cells in CRS.
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