Translational pediatrics · 2026
Obesity-related palmitic acid exacerbates IL-13-induced mucus phenotype in 16HBE airway epithelial cells via AMPK suppression.
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Liu Qingbin, Chang Xiaoyi, Jing Wei, Liu Siyu
Аннотация
BACKGROUND: Mucus hypersecretion and obesity are two prevalent comorbidities that independently worsen childhood asthma outcomes. However, the metabolic mechanisms by which obesity-related factors interact with type 2 (T2) inflammatory signals to exacerbate airway epithelial mucus phenotype remain poorly understood. This study aimed to investigate whether palmitic acid (PA), a representative obesity-related saturated fatty acid, amplifies interleukin-13 (IL-13)-induced mucus phenotype in human bronchial epithelial cells and to determine whether the AMP-activated protein kinase (AMPK) axis mediates this interaction.
METHODS: We stimulated 16HBE human bronchial epithelial cells with IL-13 (10 ng/mL, 72 h), PA (100 µM, 48 h), or combined IL-13 and PA exposure, in which PA was added during the final 48 h of IL-13 treatment. We activated AMPK pharmacologically with AICAR (1 mM) and suppressed AMPK genetically through small interfering RNA (siRNA)-mediated PRKAA1 knockdown. We quantified MUC5AC, MUC5B, CLCA1, and PRKAA1 messenger RNA (mRNA) transcripts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), measured IL-8 secretion by enzyme-linked immunosorbent assay (ELISA), assessed AMPKα, phosphorylated acetyl-CoA carboxylase (p-ACC), and acetyl-CoA carboxylase (ACC) by Western blot, and evaluated MUC5AC and zonula occludens-1 (ZO-1) localization by immunofluorescence.
RESULTS: Combined IL-13 and PA stimulation markedly elevated MUC5AC and CLCA1 mRNA and protein expression beyond IL-13 alone (P<0.001). In addition, combined stimulation further increased IL-8 secretion (P<0.001), indicating a stronger pro-inflammatory epithelial response after combining inflammatory and metabolic stimuli. In parallel, the p-ACC/ACC ratio, an indicator of AMPK activity, was lowest after combined IL-13 and PA exposure (P<0.001). AMPK activation with AICAR partially reversed MUC5AC, CLCA1, and IL-8 upregulation and restored ZO-1 continuity (P<0.001), whereas PRKAA1 knockdown further aggravated MUC5AC expression (P<0.01) and reduced p-ACC levels (P<0.05).
CONCLUSIONS: PA amplifies IL-13-induced airway epithelial mucus phenotype through suppression of the AMPK axis. AMPK may represent a potential therapeutic target for mucus hypersecretion in obesity-related childhood asthma.
METHODS: We stimulated 16HBE human bronchial epithelial cells with IL-13 (10 ng/mL, 72 h), PA (100 µM, 48 h), or combined IL-13 and PA exposure, in which PA was added during the final 48 h of IL-13 treatment. We activated AMPK pharmacologically with AICAR (1 mM) and suppressed AMPK genetically through small interfering RNA (siRNA)-mediated PRKAA1 knockdown. We quantified MUC5AC, MUC5B, CLCA1, and PRKAA1 messenger RNA (mRNA) transcripts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), measured IL-8 secretion by enzyme-linked immunosorbent assay (ELISA), assessed AMPKα, phosphorylated acetyl-CoA carboxylase (p-ACC), and acetyl-CoA carboxylase (ACC) by Western blot, and evaluated MUC5AC and zonula occludens-1 (ZO-1) localization by immunofluorescence.
RESULTS: Combined IL-13 and PA stimulation markedly elevated MUC5AC and CLCA1 mRNA and protein expression beyond IL-13 alone (P<0.001). In addition, combined stimulation further increased IL-8 secretion (P<0.001), indicating a stronger pro-inflammatory epithelial response after combining inflammatory and metabolic stimuli. In parallel, the p-ACC/ACC ratio, an indicator of AMPK activity, was lowest after combined IL-13 and PA exposure (P<0.001). AMPK activation with AICAR partially reversed MUC5AC, CLCA1, and IL-8 upregulation and restored ZO-1 continuity (P<0.001), whereas PRKAA1 knockdown further aggravated MUC5AC expression (P<0.01) and reduced p-ACC levels (P<0.05).
CONCLUSIONS: PA amplifies IL-13-induced airway epithelial mucus phenotype through suppression of the AMPK axis. AMPK may represent a potential therapeutic target for mucus hypersecretion in obesity-related childhood asthma.