The following is a summary of “Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis,” published in the APRIL 2023 issue of Allergy (& Immunology) by Chen, et al.

Glucose concentrations in nasal secretions are elevated in chronic rhinosinusitis (CRS). However, the role of glucose metabolism and its impact on disease pathogenesis in CRS remained unclear. Therefore, for a study, researchers sought to investigate glucose metabolism and its effects on nasal epithelial cell function in CRS with and without nasal polyps (CRSwNP and CRSsNP).

Glucose metabolites were analyzed using mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were measured using quantitative RT-PCR. Protein expression of GLUTs was assessed through immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was quantified using a fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured, and bioenergetic analysis was performed using a Seahorse XF analyzer. Gene expression in HNECs was profiled through RNA sequencing.

Elevated glucose concentrations in nasal secretions were confirmed in both CRSsNP and CRSwNP. HNECs showed abundant GLUT4, GLUT10, and GLUT11 expression, which was upregulated by inflammatory cytokines and D-glucose and increased in CRS. Glucose uptake, glycolysis, tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were all increased in HNECs in CRSsNP and CRSwNP, with a predominant shift towards glycolysis. 

Treatment of HNECs with high levels of apical D-glucose resulted in enhanced glucose uptake, increased glycolysis, and upregulated production of IL-1α, IL-1β, TNF-α, CCL20, and CXCL8 production. These effects were suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis.

Elevated glucose levels in nasal secretions promoted glucose uptake and favored glycolysis in epithelial cells, enhancing the proinflammatory function of these cells in CRS. The study highlighted the role of glucose metabolism in CRS and suggested its potential as a target for therapeutic intervention.

Source: jacionline.org/article/S0091-6749(22)01421-X/fulltext