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Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

β2 adrenergic agonist suppresses eosinophil-induced epithelial-to-mesenchymal transition of bronchial epithelial cells

Authors: Keigo Kainuma, Tetsu Kobayashi, Corina N. D’Alessandro-Gabazza, Masaaki Toda, Taro Yasuma, Kota Nishihama, Hajime Fujimoto, Yu Kuwabara, Koa Hosoki, Mizuho Nagao, Takao Fujisawa, Esteban C. Gabazza

Published in: Respiratory Research | Issue 1/2017

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Abstract

Background

Epithelial-mesenchymal transition is currently recognized as an important mechanism for the increased number of myofibroblasts in cancer and fibrotic diseases. We have already reported that epithelial-mesenchymal transition is involved in airway remodeling induced by eosinophils. Procaterol is a selective and full β2 adrenergic agonist that is used as a rescue of asthmatic attack inhaler form and orally as a controller. In this study, we evaluated whether procaterol can suppress epithelial-mesenchymal transition of airway epithelial cells induced by eosinophils.

Methods

Epithelial-mesenchymal transition was assessed using a co-culture system of human bronchial epithelial cells and primary human eosinophils or an eosinophilic leukemia cell line.

Results

Procaterol significantly inhibited co-culture associated morphological changes of bronchial epithelial cells, decreased the expression of vimentin, and increased the expression of E-cadherin compared to control. Butoxamine, a specific β2-adrenergic antagonist, significantly blocked changes induced by procaterol. In addition, procaterol inhibited the expression of adhesion molecules induced during the interaction between eosinophils and bronchial epithelial cells, suggesting the involvement of adhesion molecules in the process of epithelial-mesenchymal transition. Forskolin, a cyclic adenosine monophosphate-promoting agent, exhibits similar inhibitory activity of procaterol.

Conclusions

Overall, these observations support the beneficial effect of procaterol on airway remodeling frequently associated with chronic obstructive pulmonary diseases.
Literature
3.
go back to reference William W, Busse Jr aRFL. Asthma. N Engl J Med. 2001;344:351–62. William W, Busse Jr aRFL. Asthma. N Engl J Med. 2001;344:351–62.
5.
go back to reference Eldon MA, Blake DS, Coon MJ, Nordblom GD, Sedman AJ, Colburn WA. Clinical pharmacokinetics of procaterol: dose proportionality after administration of single oral doses. Biopharm Drug Dispos. 1992;13:663–9.CrossRefPubMed Eldon MA, Blake DS, Coon MJ, Nordblom GD, Sedman AJ, Colburn WA. Clinical pharmacokinetics of procaterol: dose proportionality after administration of single oral doses. Biopharm Drug Dispos. 1992;13:663–9.CrossRefPubMed
6.
go back to reference Momose T, Okubo Y, Horie S, Suzuki J, Isobe M, Sekiguchi M. Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression. Int Arch Allergy Immunol. 1998;117:138–45.CrossRefPubMed Momose T, Okubo Y, Horie S, Suzuki J, Isobe M, Sekiguchi M. Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression. Int Arch Allergy Immunol. 1998;117:138–45.CrossRefPubMed
7.
go back to reference Hanania NA, Moore RH. Anti-inflammatory activities of beta2-agonists. Curr Drug Targets Inflamm Allergy. 2004;3:271–7.CrossRefPubMed Hanania NA, Moore RH. Anti-inflammatory activities of beta2-agonists. Curr Drug Targets Inflamm Allergy. 2004;3:271–7.CrossRefPubMed
8.
go back to reference Butchers PR, Vardey CJ, Johnson M. Salmeterol: a potent and long-acting inhibitor of inflammatory mediator release from human lung. Br J Pharmacol. 1991;104:672–6.CrossRefPubMedPubMedCentral Butchers PR, Vardey CJ, Johnson M. Salmeterol: a potent and long-acting inhibitor of inflammatory mediator release from human lung. Br J Pharmacol. 1991;104:672–6.CrossRefPubMedPubMedCentral
9.
go back to reference Ezeamuzie CI, al-Hage M. Differential effects of salbutamol and salmeterol on human eosinophil responses. J Pharmacol Exp Ther. 1998;284:25–31.PubMed Ezeamuzie CI, al-Hage M. Differential effects of salbutamol and salmeterol on human eosinophil responses. J Pharmacol Exp Ther. 1998;284:25–31.PubMed
10.
go back to reference Koyama S, Sato E, Masubuchi T, Takamizawa A, Kubo K, Nagai S, Isumi T. Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity. Eur Respir J. 1999;14:767–75.CrossRefPubMed Koyama S, Sato E, Masubuchi T, Takamizawa A, Kubo K, Nagai S, Isumi T. Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity. Eur Respir J. 1999;14:767–75.CrossRefPubMed
11.
go back to reference Yamaguchi T, Nagata M, Miyazawa H, Kikuchi I, Kikuchi S, Hagiwara K, Kanazawa M. Tulobuterol, aβ2-agonist, attenuates eosinophil adhesion to endothelial cells. Allergol Intern. 2005;54:283–8.CrossRef Yamaguchi T, Nagata M, Miyazawa H, Kikuchi I, Kikuchi S, Hagiwara K, Kanazawa M. Tulobuterol, aβ2-agonist, attenuates eosinophil adhesion to endothelial cells. Allergol Intern. 2005;54:283–8.CrossRef
12.
go back to reference Ohbayashi H, Adachi M. Pretreatment with inhaled procaterol improves symptoms of dyspnea and quality of life in patients with severe COPD. Int J Gen Med. 2012;5:517–24.CrossRefPubMedPubMedCentral Ohbayashi H, Adachi M. Pretreatment with inhaled procaterol improves symptoms of dyspnea and quality of life in patients with severe COPD. Int J Gen Med. 2012;5:517–24.CrossRefPubMedPubMedCentral
13.
14.
go back to reference Ninane V, Vandevoorde J, Cataldo D, Derom E, Liistro G, Munghen E, Peche R, Schlesser M, Verleden G, Vincken W. New developments in inhaler devices within pharmaceutical companies: a systematic review of the impact on clinical outcomes and patient preferences. Respir Med. 2015;109:1430–8.CrossRefPubMed Ninane V, Vandevoorde J, Cataldo D, Derom E, Liistro G, Munghen E, Peche R, Schlesser M, Verleden G, Vincken W. New developments in inhaler devices within pharmaceutical companies: a systematic review of the impact on clinical outcomes and patient preferences. Respir Med. 2015;109:1430–8.CrossRefPubMed
15.
go back to reference Kannan R, Przekwas AJ, Singh N, Delvadia R, Tian G, Walenga R. Pharmachological aerosols deposition patterns from a dry powder inhaler: Euler Lagrangian prediction and validation. Med Eng Phys. 2017;42:35–47.CrossRef Kannan R, Przekwas AJ, Singh N, Delvadia R, Tian G, Walenga R. Pharmachological aerosols deposition patterns from a dry powder inhaler: Euler Lagrangian prediction and validation. Med Eng Phys. 2017;42:35–47.CrossRef
16.
go back to reference Kannan R, Guo P, Przekwas A. Particle transport in the human respiratory tract: formulation of a nodal inverse distance weighted Eulerian–Lagrangian transport and implementation of the Wind-Kessel algorithm for an oral delivery. Int J Numer Methods Biomed Eng. 2016;32:e02746. Kannan R, Guo P, Przekwas A. Particle transport in the human respiratory tract: formulation of a nodal inverse distance weighted Eulerian–Lagrangian transport and implementation of the Wind-Kessel algorithm for an oral delivery. Int J Numer Methods Biomed Eng. 2016;32:e02746.
17.
go back to reference Kannan R, Chen ZJ, Singh N, Przekwas A, Delvadia R, Tian G, Walenga R. A quasi-3D wire approach to model pulmonary airflow in human airways. Int J Numer Methods Biomed Eng. 2016;33:e02838. Kannan R, Chen ZJ, Singh N, Przekwas A, Delvadia R, Tian G, Walenga R. A quasi-3D wire approach to model pulmonary airflow in human airways. Int J Numer Methods Biomed Eng. 2016;33:e02838.
18.
go back to reference Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172:973–81.CrossRefPubMedPubMedCentral Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172:973–81.CrossRefPubMedPubMedCentral
19.
go back to reference Hosoki K, Kainuma K, Toda M, Harada E, Chelakkot-Govindalayathila AL, Roeen Z, Nagao M, D'Alessandro-Gabazza CN, Fujisawa T, Gabazza EC. Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils. Biochem Biophys Res Commun. 2014;449:351–6. Hosoki K, Kainuma K, Toda M, Harada E, Chelakkot-Govindalayathila AL, Roeen Z, Nagao M, D'Alessandro-Gabazza CN, Fujisawa T, Gabazza EC. Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils. Biochem Biophys Res Commun. 2014;449:351–6.
20.
go back to reference Yasukawa A, Hosoki K, Toda M, Miyake Y, Matsushima Y, Matsumoto T, Boveda-Ruiz D, Gil-Bernabe P, Nagao M, Sugimoto M, Hiraguchi Y, Tokuda R, Naito M, Takagi T, D’Alessandro-Gabazza CN, Suga S, Kobayashi T, Fujisawa T, Taguchi O, Gabazza EC. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells. PLoS ONE. 2013;8:e64281.CrossRefPubMedPubMedCentral Yasukawa A, Hosoki K, Toda M, Miyake Y, Matsushima Y, Matsumoto T, Boveda-Ruiz D, Gil-Bernabe P, Nagao M, Sugimoto M, Hiraguchi Y, Tokuda R, Naito M, Takagi T, D’Alessandro-Gabazza CN, Suga S, Kobayashi T, Fujisawa T, Taguchi O, Gabazza EC. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells. PLoS ONE. 2013;8:e64281.CrossRefPubMedPubMedCentral
21.
go back to reference Randolph TG. Blood studies in allergy; variations in eosinophiles following test feeding of foods. J Allergy. 1947;18:199–211.CrossRefPubMed Randolph TG. Blood studies in allergy; variations in eosinophiles following test feeding of foods. J Allergy. 1947;18:199–211.CrossRefPubMed
22.
go back to reference Hackett TL. Epithelial-mesenchymal transition in the pathophysiology of airway remodelling in asthma. Curr Opin Allergy Clin Immunol. 2012;12:53–9.CrossRefPubMed Hackett TL. Epithelial-mesenchymal transition in the pathophysiology of airway remodelling in asthma. Curr Opin Allergy Clin Immunol. 2012;12:53–9.CrossRefPubMed
23.
go back to reference Hackett TL, Warner SM, Stefanowicz D, Shaheen F, Pechkovsky DV, Murray LA, Argentieri R, Kicic A, Stick SM, Bai TR, Knight DA. Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1. Am J Respir Crit Care Med. 2009;180:122–33.CrossRefPubMed Hackett TL, Warner SM, Stefanowicz D, Shaheen F, Pechkovsky DV, Murray LA, Argentieri R, Kicic A, Stick SM, Bai TR, Knight DA. Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1. Am J Respir Crit Care Med. 2009;180:122–33.CrossRefPubMed
24.
go back to reference Johnson JR, Nishioka M, Chakir J, Risse PA, Almaghlouth I, Bazarbashi AN, Plante S, Martin JG, Eidelman D, Hamid Q. IL-22 contributes to TGF-beta1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells. Respir Res. 2013;14:118.CrossRefPubMedPubMedCentral Johnson JR, Nishioka M, Chakir J, Risse PA, Almaghlouth I, Bazarbashi AN, Plante S, Martin JG, Eidelman D, Hamid Q. IL-22 contributes to TGF-beta1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells. Respir Res. 2013;14:118.CrossRefPubMedPubMedCentral
25.
go back to reference Pain M, Bermudez O, Lacoste P, Royer PJ, Botturi K, Tissot A, Brouard S, Eickelberg O, Magnan A. Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype. Eur Respir Rev. 2014;23:118–30.CrossRefPubMed Pain M, Bermudez O, Lacoste P, Royer PJ, Botturi K, Tissot A, Brouard S, Eickelberg O, Magnan A. Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype. Eur Respir Rev. 2014;23:118–30.CrossRefPubMed
26.
go back to reference Yang ZC, Yi MJ, Ran N, Wang C, Fu P, Feng XY, Xu L, Qu ZH. Transforming growth factor-beta1 induces bronchial epithelial cells to mesenchymal transition by activating the Snail pathway and promotes airway remodeling in asthma. Mol Med Rep. 2013;8:1663–8.PubMed Yang ZC, Yi MJ, Ran N, Wang C, Fu P, Feng XY, Xu L, Qu ZH. Transforming growth factor-beta1 induces bronchial epithelial cells to mesenchymal transition by activating the Snail pathway and promotes airway remodeling in asthma. Mol Med Rep. 2013;8:1663–8.PubMed
27.
go back to reference Gauldie J, Bonniaud P, Sime P, Ask K, Kolb M. TGF-beta, Smad3 and the process of progressive fibrosis. Biochem Soc Trans. 2007;35:661–4.CrossRefPubMed Gauldie J, Bonniaud P, Sime P, Ask K, Kolb M. TGF-beta, Smad3 and the process of progressive fibrosis. Biochem Soc Trans. 2007;35:661–4.CrossRefPubMed
28.
go back to reference Hansel TT, Braunstein JB, Walker C, Blaser K, Bruijnzeel PL, Virchow Jr JC, Virchow Sr C. Sputum eosinophils from asthmatics express ICAM-1 and HLA-DR. Clin Exp Immunol. 1991;86:271–7.CrossRefPubMedPubMedCentral Hansel TT, Braunstein JB, Walker C, Blaser K, Bruijnzeel PL, Virchow Jr JC, Virchow Sr C. Sputum eosinophils from asthmatics express ICAM-1 and HLA-DR. Clin Exp Immunol. 1991;86:271–7.CrossRefPubMedPubMedCentral
29.
go back to reference Laudanna C, Campbell JJ, Butcher EC. Elevation of intracellular cAMP inhibits RhoA activation and integrin-dependent leukocyte adhesion induced by chemoattractants. J Biol Chem. 1997;272:24141–4.CrossRefPubMed Laudanna C, Campbell JJ, Butcher EC. Elevation of intracellular cAMP inhibits RhoA activation and integrin-dependent leukocyte adhesion induced by chemoattractants. J Biol Chem. 1997;272:24141–4.CrossRefPubMed
30.
go back to reference Hu P, Shen M, Zhang P, Zheng C, Pang Z, Zhu L, Du J. Intratumoral neutrophil granulocytes contribute to epithelial-mesenchymal transition in lung adenocarcinoma cells. Tumour Biol. 2015;36:7789–96.CrossRefPubMed Hu P, Shen M, Zhang P, Zheng C, Pang Z, Zhu L, Du J. Intratumoral neutrophil granulocytes contribute to epithelial-mesenchymal transition in lung adenocarcinoma cells. Tumour Biol. 2015;36:7789–96.CrossRefPubMed
31.
go back to reference Yang Z, Xie H, He D, Li L. Infiltrating macrophages increase RCC epithelial mesenchymal transition (EMT) and stem cell-like populations via AKT and mTOR signaling. Oncotarget. 2016;7:44478–91.PubMedPubMedCentral Yang Z, Xie H, He D, Li L. Infiltrating macrophages increase RCC epithelial mesenchymal transition (EMT) and stem cell-like populations via AKT and mTOR signaling. Oncotarget. 2016;7:44478–91.PubMedPubMedCentral
32.
go back to reference Grainge CL, Lau LCK, Ward JA, Dulay V, Lahiff G, Wilson S, Holgate S, Davies DE, Howarth PH. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med. 2011;364:2006–15. Grainge CL, Lau LCK, Ward JA, Dulay V, Lahiff G, Wilson S, Holgate S, Davies DE, Howarth PH. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med. 2011;364:2006–15.
Metadata
Title
β2 adrenergic agonist suppresses eosinophil-induced epithelial-to-mesenchymal transition of bronchial epithelial cells
Authors
Keigo Kainuma
Tetsu Kobayashi
Corina N. D’Alessandro-Gabazza
Masaaki Toda
Taro Yasuma
Kota Nishihama
Hajime Fujimoto
Yu Kuwabara
Koa Hosoki
Mizuho Nagao
Takao Fujisawa
Esteban C. Gabazza
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0563-4

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