- STAT3 inhibition decreases ATP-induced MUC8 gene expression in human airway epithelial cells
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Cheol Hong Kim, Kyoung Seob Song
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Kosin Med J. 2022;37(2):134-139. Published online June 24, 2022
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DOI: https://doi.org/10.7180/kmj.22.102
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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 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 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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Citations
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Hyun-Chae Lee, Sun-Hee Park, Hye Min Jeong, Goeun Shin, Sung In Lim, Jeongtae Kim, Jaewon Shim, Yeong-Min Park, Kyoung Seob Song eLife.2024;[Epub] CrossRef - Inhibition of Urban Particulate Matter-Induced Airway Inflammation by RIPK3 through the Regulation of Tight Junction Protein Production
Sun-Hee Park, Hyun-Chae Lee, Hye Min Jeong, Jeong-Sang Lee, Hee-Jae Cha, Cheol Hong Kim, Jeongtae Kim, Kyoung Seob Song International Journal of Molecular Sciences.2023; 24(17): 13320. CrossRef - PDZ Peptide of the ZO-1 Protein Significantly Increases UTP-Induced MUC8 Anti-Inflammatory Mucin Overproduction in Human Airway Epithelial Cells
Han Seo, Hyun-Chae Lee, Ki Chul Lee, Doosik Kim, Jiwook Kim, Donghee Kang, Hyung-Joo Chung, Hee-Jae Cha, Jeongtae Kim, Kyoung Seob Song Molecules and Cells.2023; 46(11): 700. CrossRef
- Regulatory Mechanism of Mucous Hyperproduction in the Airway
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Kyoung Seob Song
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Kosin Med J. 2010;25(2):1-5. Published online December 31, 2010
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