, Volume 40, Issue 1, pp 184–194 | Cite as

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

  • Jae-Won Lee
  • Ji-Won Park
  • Ok-Kyoung Kwon
  • Hee Jae Lee
  • Hye Gwang Jeong
  • Jae-Hong Kim
  • Sei-Ryang OhEmail author
  • Kyoung-Seop AhnEmail author


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.


chronic obstructive pulmonary disease cigarette smoke NPS2143 MUC5AC MAPKs NF-κB 



Calcium sensing receptor


Chronic obstructive pulmonary disease


Cigarette smoke extract


Mucin 5AC


Matrix-metalloproteinase 9


Interleukin 6


Tumor necrosis factor α


Mitogen-activated protein kinases


Nuclear factor-κB



This work was supported by a grant from the KRIBB Research Initiative Program (KGM 1221622) and the Ministry of Health and Welfare (HI14C1277) of the Republic of Korea.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jae-Won Lee
    • 1
  • Ji-Won Park
    • 1
  • Ok-Kyoung Kwon
    • 1
    • 2
  • Hee Jae Lee
    • 3
  • Hye Gwang Jeong
    • 2
  • Jae-Hong Kim
    • 4
  • Sei-Ryang Oh
    • 1
    Email author
  • Kyoung-Seop Ahn
    • 1
    Email author
  1. 1.Natural Medicine Research Center, Korea Research Institute of Bioscience and BiotechnologyChungju-siRepublic of Korea
  2. 2.Department of Toxicology, College of PharmacyChungnam National UniversityDaejeonRepublic of Korea
  3. 3.Department of Pharmacology, College of MedicineKangwon National UniversityChuncheonRepublic of Korea
  4. 4.Department of Life Sciences and BiotechnologyKorea UniversitySeoulRepublic of Korea

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