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Glucose metabolism is the main pathway for aryl hydrocarbon receptor (AhR) activation to down-regulate the neutrophil elastase (NE) activity. (a) The diagram of glucose metabolism. (b-e) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of lipopolysaccharide (LPS, 10 μg/mL) or phorbol-12-myristate-13-acetate (PMA, 50 nM). The levels of Magt1, Magt 2, Magt 4, Magt5 and glutamine-fructose-6-phosphate transaminase (GFPT) were detected. (f-j) The neutrophils were treated with FICZ (100 nM) at the present or absence of LPS (10 μg/mL), and the intracellular metabolites were detected using a high-resolution <t>nuclear</t> <t>magnetic</t> resonance <t>(NMR).</t> The results were analyzed by PCA (f) , PLS (g) , OPLS (h) , KEGG enrichment analysis (i) and cluster analysis (j) . (k, l) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM). The relative glucose uptake (k) and intracellular pH values (l) were determined. (m, n) The neutrophils were treated with FICZ (100 nM) or DIM (10 μM) alone or in combination with L-sodium lactate (20 mM), ATP (100 μM) or GlcNAc (20 mM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM), and the release of dsDNA (m) and NE activity (n) was determined. The data were presented as the means ± S.E.M. of three or five independent experiments. ## p < 0.01 vs. Control group; * p < 0.05, ** p < 0.01 vs. LPS group; $$ p < 0.01 vs. LPS + FICZ group; ++ p < 0.01 vs. LPS + DIM group.
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Glucose metabolism is the main pathway for aryl hydrocarbon receptor (AhR) activation to down-regulate the neutrophil elastase (NE) activity. (a) The diagram of glucose metabolism. (b-e) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of lipopolysaccharide (LPS, 10 μg/mL) or phorbol-12-myristate-13-acetate (PMA, 50 nM). The levels of Magt1, Magt 2, Magt 4, Magt5 and glutamine-fructose-6-phosphate transaminase (GFPT) were detected. (f-j) The neutrophils were treated with FICZ (100 nM) at the present or absence of LPS (10 μg/mL), and the intracellular metabolites were detected using a high-resolution <t>nuclear</t> <t>magnetic</t> resonance <t>(NMR).</t> The results were analyzed by PCA (f) , PLS (g) , OPLS (h) , KEGG enrichment analysis (i) and cluster analysis (j) . (k, l) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM). The relative glucose uptake (k) and intracellular pH values (l) were determined. (m, n) The neutrophils were treated with FICZ (100 nM) or DIM (10 μM) alone or in combination with L-sodium lactate (20 mM), ATP (100 μM) or GlcNAc (20 mM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM), and the release of dsDNA (m) and NE activity (n) was determined. The data were presented as the means ± S.E.M. of three or five independent experiments. ## p < 0.01 vs. Control group; * p < 0.05, ** p < 0.01 vs. LPS group; $$ p < 0.01 vs. LPS + FICZ group; ++ p < 0.01 vs. LPS + DIM group.
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Glucose metabolism is the main pathway for aryl hydrocarbon receptor (AhR) activation to down-regulate the neutrophil elastase (NE) activity. (a) The diagram of glucose metabolism. (b-e) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of lipopolysaccharide (LPS, 10 μg/mL) or phorbol-12-myristate-13-acetate (PMA, 50 nM). The levels of Magt1, Magt 2, Magt 4, Magt5 and glutamine-fructose-6-phosphate transaminase (GFPT) were detected. (f-j) The neutrophils were treated with FICZ (100 nM) at the present or absence of LPS (10 μg/mL), and the intracellular metabolites were detected using a high-resolution <t>nuclear</t> <t>magnetic</t> resonance <t>(NMR).</t> The results were analyzed by PCA (f) , PLS (g) , OPLS (h) , KEGG enrichment analysis (i) and cluster analysis (j) . (k, l) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM). The relative glucose uptake (k) and intracellular pH values (l) were determined. (m, n) The neutrophils were treated with FICZ (100 nM) or DIM (10 μM) alone or in combination with L-sodium lactate (20 mM), ATP (100 μM) or GlcNAc (20 mM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM), and the release of dsDNA (m) and NE activity (n) was determined. The data were presented as the means ± S.E.M. of three or five independent experiments. ## p < 0.01 vs. Control group; * p < 0.05, ** p < 0.01 vs. LPS group; $$ p < 0.01 vs. LPS + FICZ group; ++ p < 0.01 vs. LPS + DIM group.
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Glucose metabolism is the main pathway for aryl hydrocarbon receptor (AhR) activation to down-regulate the neutrophil elastase (NE) activity. (a) The diagram of glucose metabolism. (b-e) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of lipopolysaccharide (LPS, 10 μg/mL) or phorbol-12-myristate-13-acetate (PMA, 50 nM). The levels of Magt1, Magt 2, Magt 4, Magt5 and glutamine-fructose-6-phosphate transaminase (GFPT) were detected. (f-j) The neutrophils were treated with FICZ (100 nM) at the present or absence of LPS (10 μg/mL), and the intracellular metabolites were detected using a high-resolution <t>nuclear</t> <t>magnetic</t> resonance <t>(NMR).</t> The results were analyzed by PCA (f) , PLS (g) , OPLS (h) , KEGG enrichment analysis (i) and cluster analysis (j) . (k, l) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM). The relative glucose uptake (k) and intracellular pH values (l) were determined. (m, n) The neutrophils were treated with FICZ (100 nM) or DIM (10 μM) alone or in combination with L-sodium lactate (20 mM), ATP (100 μM) or GlcNAc (20 mM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM), and the release of dsDNA (m) and NE activity (n) was determined. The data were presented as the means ± S.E.M. of three or five independent experiments. ## p < 0.01 vs. Control group; * p < 0.05, ** p < 0.01 vs. LPS group; $$ p < 0.01 vs. LPS + FICZ group; ++ p < 0.01 vs. LPS + DIM group.
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Glucose metabolism is the main pathway for aryl hydrocarbon receptor (AhR) activation to down-regulate the neutrophil elastase (NE) activity. (a) The diagram of glucose metabolism. (b-e) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of lipopolysaccharide (LPS, 10 μg/mL) or phorbol-12-myristate-13-acetate (PMA, 50 nM). The levels of Magt1, Magt 2, Magt 4, Magt5 and glutamine-fructose-6-phosphate transaminase (GFPT) were detected. (f-j) The neutrophils were treated with FICZ (100 nM) at the present or absence of LPS (10 μg/mL), and the intracellular metabolites were detected using a high-resolution nuclear magnetic resonance (NMR). The results were analyzed by PCA (f) , PLS (g) , OPLS (h) , KEGG enrichment analysis (i) and cluster analysis (j) . (k, l) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM). The relative glucose uptake (k) and intracellular pH values (l) were determined. (m, n) The neutrophils were treated with FICZ (100 nM) or DIM (10 μM) alone or in combination with L-sodium lactate (20 mM), ATP (100 μM) or GlcNAc (20 mM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM), and the release of dsDNA (m) and NE activity (n) was determined. The data were presented as the means ± S.E.M. of three or five independent experiments. ## p < 0.01 vs. Control group; * p < 0.05, ** p < 0.01 vs. LPS group; $$ p < 0.01 vs. LPS + FICZ group; ++ p < 0.01 vs. LPS + DIM group.

Journal: Journal of Advanced Research

Article Title: Aryl hydrocarbon receptor impairs HK2-controlled flux of the hexosamine biosynthesis pathway to suppress NETosis in an N -glycosylation-dependent manner

doi: 10.1016/j.jare.2025.06.078

Figure Lengend Snippet: Glucose metabolism is the main pathway for aryl hydrocarbon receptor (AhR) activation to down-regulate the neutrophil elastase (NE) activity. (a) The diagram of glucose metabolism. (b-e) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of lipopolysaccharide (LPS, 10 μg/mL) or phorbol-12-myristate-13-acetate (PMA, 50 nM). The levels of Magt1, Magt 2, Magt 4, Magt5 and glutamine-fructose-6-phosphate transaminase (GFPT) were detected. (f-j) The neutrophils were treated with FICZ (100 nM) at the present or absence of LPS (10 μg/mL), and the intracellular metabolites were detected using a high-resolution nuclear magnetic resonance (NMR). The results were analyzed by PCA (f) , PLS (g) , OPLS (h) , KEGG enrichment analysis (i) and cluster analysis (j) . (k, l) The neutrophils were treated with FICZ (100 nM), DIM (10 μM) or CH223191 (10 μM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM). The relative glucose uptake (k) and intracellular pH values (l) were determined. (m, n) The neutrophils were treated with FICZ (100 nM) or DIM (10 μM) alone or in combination with L-sodium lactate (20 mM), ATP (100 μM) or GlcNAc (20 mM) at the present or absence of LPS (10 μg/mL) or PMA (50 nM), and the release of dsDNA (m) and NE activity (n) was determined. The data were presented as the means ± S.E.M. of three or five independent experiments. ## p < 0.01 vs. Control group; * p < 0.05, ** p < 0.01 vs. LPS group; $$ p < 0.01 vs. LPS + FICZ group; ++ p < 0.01 vs. LPS + DIM group.

Article Snippet: The collected nuclear magnetic resonance (NMR) spectra were analysed using Chenomx NMR Suite software, and statistical analysis with data visualisation was performed using the MetaboAnalyst platform.

Techniques: Activation Assay, Activity Assay, Nuclear Magnetic Resonance, Control