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KMID : 1141320220370020134
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Kosin Medical Journal
2022 Volume.37 No. 2 p.134 ~ p.139
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STAT3 inhibition decreases ATP-induced MUC8 gene expression in human airway epithelial cells
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Kim Cheol-Hong
Song Kyoung-Seob
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Abstract
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Background: Contact between the human pulmonary system and bacteria, viruses, or other pathogens can induce airway diseases. Although pathogen-induced mucus oversecretion and hyperproduction are frequently observed in the human respiratory tract, the molecular mechanisms of pathogen-induced mucus hypersecretion and overproduction remain unclear. The objective of this study was to investigate the physiological signaling mechanism of adenosine triphosphate (ATP)-induced MUC8 gene expression in human airway epithelial cells.
Methods: Real-time reverse transcription polymerase chain reaction, a cytokine array, and a Ca2+ concentration assay were performed to investigate the ATP/P2Y2-induced MUC8 gene expression levels in human airway epithelial cells.
Results: The ATP/P2Y2 complex robustly secreted interleukin (IL)-6 in a time-dependent manner, whereas siRNA-P2Y2 did not. Moreover, ATP/P2Y2 induced MUC8 gene expression. IL-6 secreted by ATP strongly elevated ATP/P2Y2-induced MUC8 gene expression compared to ATP/P2Y2. Interestingly, a specific signal transducer and activator of transcription 3 (STAT3) inhibitor, 5,15-DPP, dramatically inhibited ATP/P2Y2/IL-6-induced STAT3 phosphorylation and resulted in an approximately 5-fold decrease in MUC8 gene expression.
Conclusions: We showed that IL-6-activated STAT6 is essential for ATP/P2Y2-induced MUC8 gene expression as part of inflammatory signaling by cytokines during airway inflammation. Our results provide a new molecular understanding of the signaling mechanism of MUC8 gene expression during airway inflammation.
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KEYWORD
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Airway, Inflammation, Adenosine triphosphate, Mucin 8, STAT3 transcription factor
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