NPS2143 Inhibits MUC5AC and Proinflammatory Mediators in Cigarette Smoke Extract (CSE)-Stimulated Human Airway Epithelial Cells

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• 作者：Jae-Won Lee ; Ji-Won Park ; Ok-Kyoung Kwon ; Hee Jae Lee ; Hye Gwang Jeong…
• 关键词：KEY WORDSchronic obstructive pulmonary disease ; cigarette smoke ; NPS2143 ; MUC5AC ; MAPKs ; NF ; κB
• 刊名：Inflammation
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：40
• 期：1
• 页码：184-194
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Rheumatology; Internal Medicine; Pharmacology/Toxicology; Pathology;
• 出版者：Springer US
• ISSN：1573-2576
• 卷排序：40

文摘

Mucus overproduction is a fundamental hallmark of COPD that is caused by exposure to cigarette smoke. MUC5AC is one of the main mucin genes expressed in the respiratory epithelium, and its transcriptional upregulation often correlates with increased mucus secretion. Calcium-sensing receptor (CaSR) antagonists have been reported to possess anti-inflammatory effects. The purpose of the present study was to investigate the protective role of NPS2143, a selective CaSR antagonist on cigarette smoke extract (CSE)-stimulated NCI-H292 mucoepidermoid human lung cells. Treatment of NPS2143 significantly inhibited the expression of MUC5AC in CSE-stimulated H292 cells. NPS2143 reduced the expression of MMP-9 in CSE-stimulated H292 cells. NPS2143 also decreased the release of proinflammatory cytokines such as IL-6 and TNF-α in CSE-stimulated H292 cells. Furthermore, NPS2143 attenuated the activation of MAPKs (JNK, p38, and ERK) and inhibited the nuclear translocation of NF-κB in CSE-stimulated H292 cells. These results indicate that NPS2143 had a therapeutic potential in COPD.