Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells

Background and Objectives Nicotine is oxidized into tobacco-specific nitrosamines (TSNAs; NAB, NAT, NNN, NNAL, NNK) at high temperature and high pressure. TSNAs are associated with airway diseases characterized by mucus hypersecretion as a major pathophysiologic phenomenon. The aim of study is to in...

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Main Authors: Soyoung Kwak, Yoon Seok Choi, Hyung Gyun Na, Chang Hoon Bae, Si-Youn Song, Yong-Dae Kim
Format: Article
Language:English
Published: Korean Rhinologic Society 2020-05-01
Series:Journal of Rhinology
Subjects:
Online Access:http://www.j-rhinology.org/upload/pdf/jr-2019-00301.pdf
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author Soyoung Kwak
Yoon Seok Choi
Hyung Gyun Na
Chang Hoon Bae
Si-Youn Song
Yong-Dae Kim
author_facet Soyoung Kwak
Yoon Seok Choi
Hyung Gyun Na
Chang Hoon Bae
Si-Youn Song
Yong-Dae Kim
author_sort Soyoung Kwak
collection DOAJ
description Background and Objectives Nicotine is oxidized into tobacco-specific nitrosamines (TSNAs; NAB, NAT, NNN, NNAL, NNK) at high temperature and high pressure. TSNAs are associated with airway diseases characterized by mucus hypersecretion as a major pathophysiologic phenomenon. The aim of study is to investigate the effect of TSNAs on mucin overexpression and its molecular mechanism in human airway epithelial cells. Materials and Method The cytotoxicity of TSNAs was evaluated using EX-Cytox and inverted microscopy. The mRNA and protein levels of MUC5AC and MUC5B were measured using real-time PCR and ELISA. Results NAB, NNN, NNAL, and NNK did not affect cell viability. NAT did not affect cell viability up to a concentration of 100 μM in human airway epithelial cells. NAT, NNN, NNAL, and NNK significantly induced MUC5AC expression, but not MUC5B expression. NAB did not affect the expression of MUC5AC and MUC5B. Propranolol (a β-adrenergic receptor antagonist) inhibited NAT, NNN, NNAL, and NNK-induced MUC5AC expression, whereas α-bungarotoxin (an α7-nicotinic acetylcholine receptor antagonist) only inhibited NNN- and NNK-induced MUC5AC expression. Conclusion These results suggested that NAT, NNN, NNAL, and NNK induce MUC5AC expression through β-adrenergic receptor and/or α7-nicotinic acetylcholine receptor in human airway epithelial cells, which may be involved in mucus hypersecretion in inflammatory airway diseases.
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spelling doaj.art-135cfd50e98b460195caaea29872a4142022-12-22T00:01:53ZengKorean Rhinologic SocietyJournal of Rhinology1229-14982384-43612020-05-01271344010.18787/jr.2019.00301678Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial CellsSoyoung Kwak0Yoon Seok Choi1Hyung Gyun Na2Chang Hoon Bae3Si-Youn Song4Yong-Dae Kim5Department of Medical Science, College of Medicine, Graduate School of Yeungnam University, Daegu, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, KoreaBackground and Objectives Nicotine is oxidized into tobacco-specific nitrosamines (TSNAs; NAB, NAT, NNN, NNAL, NNK) at high temperature and high pressure. TSNAs are associated with airway diseases characterized by mucus hypersecretion as a major pathophysiologic phenomenon. The aim of study is to investigate the effect of TSNAs on mucin overexpression and its molecular mechanism in human airway epithelial cells. Materials and Method The cytotoxicity of TSNAs was evaluated using EX-Cytox and inverted microscopy. The mRNA and protein levels of MUC5AC and MUC5B were measured using real-time PCR and ELISA. Results NAB, NNN, NNAL, and NNK did not affect cell viability. NAT did not affect cell viability up to a concentration of 100 μM in human airway epithelial cells. NAT, NNN, NNAL, and NNK significantly induced MUC5AC expression, but not MUC5B expression. NAB did not affect the expression of MUC5AC and MUC5B. Propranolol (a β-adrenergic receptor antagonist) inhibited NAT, NNN, NNAL, and NNK-induced MUC5AC expression, whereas α-bungarotoxin (an α7-nicotinic acetylcholine receptor antagonist) only inhibited NNN- and NNK-induced MUC5AC expression. Conclusion These results suggested that NAT, NNN, NNAL, and NNK induce MUC5AC expression through β-adrenergic receptor and/or α7-nicotinic acetylcholine receptor in human airway epithelial cells, which may be involved in mucus hypersecretion in inflammatory airway diseases.http://www.j-rhinology.org/upload/pdf/jr-2019-00301.pdftobacco-specific nitrosaminesmuc5achuman airway epithelial cell
spellingShingle Soyoung Kwak
Yoon Seok Choi
Hyung Gyun Na
Chang Hoon Bae
Si-Youn Song
Yong-Dae Kim
Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells
Journal of Rhinology
tobacco-specific nitrosamines
muc5ac
human airway epithelial cell
title Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells
title_full Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells
title_fullStr Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells
title_full_unstemmed Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells
title_short Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells
title_sort effect of tobacco specific nitrosamines on muc5ac expression in human airway epithelial cells
topic tobacco-specific nitrosamines
muc5ac
human airway epithelial cell
url http://www.j-rhinology.org/upload/pdf/jr-2019-00301.pdf
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AT changhoonbae effectoftobaccospecificnitrosaminesonmuc5acexpressioninhumanairwayepithelialcells
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