STAT3 inhibition decreases ATP-induced MUC8 gene expression in human airway epithelial cells / 고신대학교의과대학학술지

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.

Sulindac Sulfide-induced Apoptosis is Caspase 3-Dependent in Maxillary Cancer Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Head and neck cancer is the sixth most common cancer in human body. Squamous cell cancer (SCC) accounts for most of sinonasal cancers. Prediction of cancer development and induction of cell death are thought to account for the conquest of maxillary sinus cancer. Little is known about its biochemical mechanism(s) of cell death. Recently, human epidemiological and clinical intervention indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase (COX) inhibitor have chemopreventive activity against colorectal cancer. We examined what kind of NSAIDs induce death of maxillary sinus cancer cells. MATERIALS AND METHOD: Human maxillary sinus cancer cells were treated with NSAIDs. The NSAIDs-induced cell death was measured by Flow cytometry (FACS). To know whether sulindac sulfide-induced cell death is apoptosis or necrosis, we carried out Western blot analysis using anti-poly ADP-ribosyl polymerase (PARP) IgG and caspase 3 assay. We also measured cell survival rate using general caspases inhibitor, Z-VAD-fmk. RESULTS: Treatment of human maxillary sinus cancer cells with sulindac sulfide resulted in a dose-dependent cell death, and induction of apoptosis. General caspases inhibitor, Z-VAD-fmk potentiated the apoptosis inhibitory effect of sulindac sulfide. CONCLUSION: These results suggest that the inhibition of caspases is responsible for a part of the induction of apoptosis by sulindac sulfide. Inhibition of caspase 3 activity may, therefore, be a useful biochemical target for the development of chemopreventive and chemotherapeutic drugs for maxillary sinus cancer.