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 Oh; Kyoung Seop Ahn

doi:10.1007/s10753-016-0468-2

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 Oh, Kyoung Seop Ahn

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

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.

Original language	English
Pages (from-to)	184-194
Number of pages	11
Journal	Inflammation
Volume	40
Issue number	1
DOIs	https://doi.org/10.1007/s10753-016-0468-2
Publication status	Published - 2017 Feb 1

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2016, Springer Science+Business Media New York.

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1007/s10753-016-0468-2

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

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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note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2016, Springer Science+Business Media New York.",

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AU - Lee, Hee Jae

AU - Jeong, Hye Gwang

AU - Kim, Jae Hong

AU - Oh, Sei Ryang

AU - Ahn, Kyoung Seop

N1 - Funding Information: 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. Publisher Copyright: © 2016, Springer Science+Business Media New York.

PY - 2017/2/1

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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