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

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Abstract

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.

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Abbreviations

CaSR:

Calcium sensing receptor

COPD:

Chronic obstructive pulmonary disease

CSE:

Cigarette smoke extract

MUC5AC:

Mucin 5AC

MMP-9:

Matrix-metalloproteinase 9

IL-6:

Interleukin 6

TNF-α:

Tumor necrosis factor α

MAPKs:

Mitogen-activated protein kinases

NF-κB:

Nuclear factor-κB

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Acknowledgments

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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    1. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk, 363-883, Republic of Korea

      Jae-Won Lee, Ji-Won Park, Ok-Kyoung Kwon, Sei-Ryang Oh & Kyoung-Seop Ahn

    2. Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, 305-764, Republic of Korea

      Ok-Kyoung Kwon & Hye Gwang Jeong

    3. Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon, 200-701, Republic of Korea

      Hee Jae Lee

    4. Department of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul, 136-701, Republic of Korea

      Jae-Hong Kim

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    1. Jae-Won Lee
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    Correspondence to Sei-Ryang Oh or Kyoung-Seop Ahn.

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    Jae-Won Lee and Ji-Won Park contributed equally to this work.

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    Lee, JW., Park, JW., Kwon, OK. et al. NPS2143 Inhibits MUC5AC and Proinflammatory Mediators in Cigarette Smoke Extract (CSE)-Stimulated Human Airway Epithelial Cells. Inflammation 40, 184–194 (2017). https://doi.org/10.1007/s10753-016-0468-2

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