Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Drugs
Erschienen in: Drugs 1/2015

01.01.2015 | Leading Article

Airway and Lung Remodelling in Chronic Pulmonary Obstructive Disease: A Role for Muscarinic Receptor Antagonists?

verfasst von: Michael Roth

Erschienen in: Drugs | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Lung tissue remodelling in chronic inflammatory lung diseases has long been regarded as a follow-up event to inflammation. Recent studies have indicated that, although airway and lung tissue remodelling is often independent of inflammation, it precedes or causes inflammation. None of the available therapies has a significant effect on airway and lung tissue remodelling in asthma, bronchiectasis, fibrosis and chronic obstructive pulmonary disease (COPD). The goal of stopping or reversing lung tissue remodelling is difficult, as the term summarizes the net effect of independent events, including (1) cell proliferation, (2) cell volume increase, (3) cell migration, (4) modified deposition and metabolism of specific extracellular matrix components, and (5) local action of infiltrated inflammatory cells. The extracellular matrix of the lung has a very high turnover, and thus small changes may accumulate to significant structural pathologies, which seem to be irreversible. The most important question is ‘why are pathological changes of the lung structure irreversible and resistant to drugs?’ Many drugs have the potential to reduce remodelling mechanisms in vitro but fail in clinical trials. New evidence suggests that muscarinic receptor inhibitors have the potential to improve lung function through modifying tissue remodelling. However, the role of muscarinic receptors in lung remodelling, especially their supportive role for other remodelling driving factors, needs to be further investigated. The focus of this review is the role of muscarinic receptors in lung tissue remodelling as it has been reported in the human lung.
Literatur
1.
2.
Postma DS, Reddel HK, ten Hacken NH, van den Berge M. Asthma and chronic obstructive pulmonary disease: similarities and differences. Clin Chest Med. 2014;35:143–56.PubMedCrossRef
3.
Sohal SS, Ward C, Danial W, Wood-Baker R, Walters EH. Recent advances in understanding inflammation and remodeling in the airways in chronic obstructive pulmonary disease. Expert Rev Respir Med. 2013;7:275–88.PubMedCrossRef
4.
5.
Foley AR, Quijano-Roy S, Collins J, Straub V, McCallum M, Deconinck N, Mercuri E, Pane M, D’Amico A, Bertini E, North K, Ryan MM, Richard P, Allamand V, Hicks D, Lamandé S, Hu Y, Gualandi F, Auh S, Muntoni F, Bönnemann CG. Natural history of pulmonary function in collagen VI-related myopathies. Brain. 2013;136:3625–33.PubMedCentralPubMedCrossRef
6.
Ghaedi M, Calle EA, Mendez JJ, Gard AL, Balestrini J, Booth A, Bove PF, Gui L, White ES, Niklason LE. Human iPS cell-derived alveolar epithelium repopulates lung extracellular matrix. J Clin Invest. 2013;123:4950–62.PubMedCentralPubMedCrossRef
7.
Parker MW, Rossi D, Peterson M, Smith K, Sikström K, White ES, Connett JE, Henke CA, Larsson O, Bitterman PB. Fibrotic extracellular matrix activates a profibrotic positive feedback loop. J Clin Invest. 2014;124:1622–35.PubMedCentralPubMedCrossRef
8.
Grainge CL, Lau LC, 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.PubMedCrossRef
9.
Grainge C, Howarth PH. Repeated high-dose inhalation allergen challenge in asthma. Clin Respir J. 2011;5:150–5.PubMedCrossRef
10.
Senhorini A, Ferreira DS, Shiang C, Silva LF, Dolhnikoff M, Gelb AF, Mauad T. Airway dimensions in fatal asthma and fatal COPD: overlap in older patients. COPD. 2013;10:348–56.PubMedCrossRef
11.
Kosciuch J, Krenke R, Gorska K, Zukowska M, Maskey-Warzechowska M, Chazan R. Airway dimensions in asthma and COPD in high resolution computed tomography: can we see the difference? Respir Care. 2013;58:1335–42.PubMedCrossRef
12.
Wright JL, Postma DS, Kerstjens HA, Timens W, Whittaker P, Churg A. Airwayremodeling in the smoke exposed guinea pig model. Inhal Toxicol. 2007;19:915–23.PubMedCrossRef
13.
Evans MJ, Fanucchi MV, Plopper CG, Hyde DM. Postnatal development of the lamina reticularis in primate airways. Anat Rec (Hoboken). 2010;293(6):947-54. doi:10.​1002/​ar.​20824.
14.
Plopper CG, Hyde DM. The non-human primate as a model for studying COPD andasthma. Pulm Pharmacol Ther. 2008;21:755–66.PubMedCrossRef
15.
16.
Fricker M, Deane A, Hansbro PM. Animal models of chronic obstructive pulmonary disease. Expert Opin Drug Discov. 2014;9:629–45.PubMedCrossRef
17.
18.
Mak JC, Baraniuk JN, Barnes PJ. Localization of muscarinic receptor subtype mRNAs in human lung. Am J Respir Cell Mol Biol. 1992;7:344–8.PubMedCrossRef
19.
Ikeda T, Anisuzzaman AS, Yoshiki H, Sasaki M, Koshiji T, Uwada J, Nishimune A, Itoh H, Muramatsu I. Regional quantification of muscarinic acetylcholine receptors and β-adrenoceptors in human airways. Br J Pharmacol. 2012;166:1804–14.PubMedCentralPubMedCrossRef
20.
Kistemaker LE, Oenema TA, Meurs H, Gosens R. Regulation of airway inflammation and remodeling by muscarinic receptors: perspectives on anticholinergic therap in asthma and COPD. Life Sci. 2012;91:1126–33.PubMedCrossRef
21.
Plopper CG, Smiley-Jewell SM, Miller LA, Fanucchi MV, Evans MJ, Buckpitt AR, Avdalovic M, Gershwin LJ, Joad JP, Kajekar R, Larson S, Pinkerton KE, Van Winkle LS, Schelegle ES, Pieczarka EM, Wu R, Hyde DM. Asthma/allergic airways disease:does postnatal exposure to environmental toxicants promote airway pathobiology? Toxicol Pathol. 2007;35:97–110.PubMedCrossRef
22.
Nordgren TM, Wyatt TA, Sweeter J, Bailey KL, Poole JA, Heires AJ, Sisson JH, Romberger DJ. Motile cilia harbor serum response factor as a mechanism of environment sensing and injury response in the airway. Am J Physiol Lung Cell Mol Physiol. 2014;306:L829–39.PubMedCrossRef
23.
Hessel J, Heldrich J, Fuller J, Staudt MR, Radisch S, Hollmann C, Harvey BG, Kaner RJ, Salit J, Yee-Levin J, Sridhar S, Pillai S, Hilton H, Wolff G, Bitter H, Visvanathan S, Fine J, Stevenson CS, Crystal RG, Tilley AE. Intraflagellar transport gene expression associated with short cilia in smoking and COPD. PLoS One. 2014;9:e85453.PubMedCentralPubMedCrossRef
24.
Klein MK, Haberberger RV, Hartmann P, Faulhammer P, Lips KS, Krain B, Wess J, Kummer W, König P. Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development. Eur Respir J. 2009;33:1113–21.PubMedCentralPubMedCrossRef
25.
Choi JY, Joo NS, Krouse ME, Wu JV, Robbins RC, Ianowski JP, Hanrahan JW, Wine JJ. Synergistic airway gland mucus secretion in response to vasoactive intestinalpeptide and carbachol is lost in cystic fibrosis. J Clin Invest. 2007;117:3118–27.PubMedCentralPubMedCrossRef
26.
27.
Aguayo SM. Determinants of susceptibility to cigarette smoke. Potential roles for neuroendocrine cells and neuropeptides in airway inflammation, airway wall remodeling, and chronic airflow obstruction. Am J Respir Crit Care Med. 1994;149:1692–8.PubMedCrossRef
28.
29.
30.
Kong KC, Butcher AJ, McWilliams P, Jones D, Wess J, Hamdan FF, Werry T, Rosethorne EM, Charlton SJ, Munson SE, Cragg HA, Smart AD, Tobin AB. M3-muscarinic receptor promotes insulin release via receptor phosphorylation/arrestin-dependent activation of protein kinase D1. Proc Natl Acad Sci USA. 2010;107:21181–6.PubMedCentralPubMedCrossRef
31.
Jiang X, Sinnett-Smith J, Rozengurt E. Carbachol induces p70S6K1 activation through an ERK-dependent but Akt-independent pathway in human colonic epithelial cells. Biochem Biophys Res Commun. 2009;387:521–4.PubMedCentralPubMedCrossRef
32.
Profita M, Bonanno A, Montalbano AM, Ferraro M, Siena L, Bruno A, Girbino S, Albano GD, Casarosa P, Pieper MP, Gjomarkaj M. Cigarette smoke extract activates human bronchial epithelial cells affecting non-neuronal cholinergic system signalling in vitro. Life Sci. 2011;89:36–43.PubMedCrossRef
33.
Tsutsumi H, Ohsaki M, Seki K, Chiba S. Respiratory syncytial virus infection of human respiratory epithelial cells enhances both muscarinic and beta2-adrenergic receptor gene expression. Acta Virol. 1999;43:267–70.PubMed
34.
Golkar L, Yarkony KA, Fryer AD. Inhibition of neuronal M(2) muscarinic receptor function in the lungs by extracellular nitric oxide. Br J Pharmacol. 2000;131:312–8.PubMedCentralPubMedCrossRef
35.
Gras D, Chanez P, Vachier I, Petit A, Bourdin A. Bronchial epithelium as a target for innovative treatments in asthma. Pharmacol Ther. 2013;140:290–305.PubMedCrossRef
36.
Park HJ, Ward SM, Desgrosellier JS, Georgescu SP, Papageorge AG, Zhuang X, Barnett JV, Galper JB. Transforming growth factor beta regulates the expression of the M2 muscarinic receptor in atrial myocytes via an effect on RhoA and p190RhoGAP. J Biol Chem. 2006;281:19995–20002.PubMedCrossRef
37.
Nie Z, Scott GD, Weis PD, Itakura A, Fryer AD, Jacoby DB. Role of TNF-α in virus-induced airway hyperresponsiveness and neuronal M2 muscarinic receptor dysfunction. Br J Pharmacol. 2011;164:444–52.PubMedCentralPubMedCrossRef
38.
Suzaki I, Asano K, Shikama Y, Hamasaki T, Kanei A, Suzaki H. Suppression of IL-8 production from airway cells by tiotropium bromide in vitro. Int J Chron Obstruct Pulmon Dis. 2011;6:439–48.PubMedCentralPubMed
39.
Profita M, Bonanno A, Siena L, Ferraro M, Montalbano AM, Pompeo F, Riccobono L, Pieper MP, Gjomarkaj M. Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB/ERK-dependent mechanism. Eur J Pharmacol. 2008;582(1–3):145–53.PubMedCrossRef
40.
Roskoski R Jr. ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res. 2012;66:105–43.PubMedCrossRef
41.
Jiménez E, Gámez MI, Bragado MJ, Montiel M. Muscarinic activation of mitogen-activated protein kinase in rat thyroid epithelial cells. Cell Signal. 2002;14:665–72.PubMedCrossRef
42.
Arrighi N, Bodei S, Lucente A, Michel MC, Zani D, Simeone C, Cunico SC, Spano P, Sigala S. Muscarinic receptors stimulate cell proliferation in the human urothelium-derived cell line UROtsa. Pharmacol Res. 2011;64:420–5.PubMedCrossRef
43.
Proskocil BJ, Sekhon HS, Jia Y, Savchenko V, Blakely RD, Lindstrom J, Spindel ER. Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells. Endocrinology. 2004;145:2498–506.PubMedCrossRef
44.
Profita M, Albano GD, Montalbano AM, Di Sano C, Anzalone G, Gagliardo R, Riccobono L, Bonanno A, Siena L, Pieper MP, Gjomarkaj M. Acetylcholine leads to signal transducer and activator of transcription 1 (STAT-1) mediated oxidative/nitrosative stress in human bronchial epithelial cell line. Biochim Biophys Acta. 2013;1832:1949–58.PubMedCrossRef
45.
Evans MJ, Fanucchi MV, Plopper CG, Hyde DM. Postnatal development of the lamina reticularis in primate airways. Anat Rec (Hoboken). 2010;293:947–54.CrossRef
46.
Royce SG, Tan L, Koek AA, Tang ML. Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma. Ann Allergy Asthma Immunol. 2009;102:238–46.PubMedCrossRef
47.
André C, Marullo S, Convents A, Lü BZ, Guillet JG, Hoebeke J, Strosberg DA. A human embryonic lung fibroblast with a high density of muscarinic acetylcholine receptors. Eur J Biochem. 1988;171:401–7.PubMedCrossRef
48.
Profita M, Bonanno A, Siena L, Bruno A, Ferraro M, Montalbano AM, Albano GD, Riccobono L, Casarosa P, Pieper MP, Gjomarkaj M. Smoke, choline acetyltransferase, muscarinic receptors, and fibroblast proliferation in chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2009;329:753–63.PubMedCrossRef
49.
Milara J, Serrano A, Peiró T, Gavaldà A, Miralpeix M, Morcillo EJ, Cortijo J. Aclidinium inhibits human lung fibroblast to myofibroblast transition. Thorax. 2012;67:229–37.PubMedCentralPubMedCrossRef
50.
Matthiesen S, Bahulayan A, Holz O, Racké K. MAPK pathway mediates muscarinic receptor-induced human lung fibroblast proliferation. Life Sci. 2007;80:2259–62.PubMedCrossRef
51.
Pieper MP, Chaudhary NI, Park JE. Acetylcholine-induced proliferation of fibroblasts and myofibroblasts in vitro is inhibited by tiotropium bromide. Life Sci. 2007;80:2270–3.PubMedCrossRef
52.
Ahmedat AS, Warnken M, Seemann WK, Mohr K, Kostenis E, Juergens UR, Racké K. Pro-fibrotic processes in human lung fibroblasts are driven by an autocrine/paracrine endothelinergic system. Br J Pharmacol. 2013;168:471–87.PubMedCentralPubMedCrossRef
53.
Ahmedat AS, Warnken M, Juergens UR, Paul Pieper M, Racké K. β2-adrenoceptors and muscarinic receptors mediate opposing effects on endothelin-1 expression in human lung fibroblasts. Eur J Pharmacol. 2012;691:218–24.PubMedCrossRef
54.
Haag S, Matthiesen S, Juergens UR, Racké K. Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts. Eur Respir J. 2008;32:555–62.PubMedCrossRef
55.
Tang JM, Yuan J, Li Q, Wang JN, Kong X, Zheng F, Zhang L, Chen L, Guo LY, Huang YH, Yang JY, Chen SY. Acetylcholine induces mesenchymal stem cell migration via Ca2+/PKC/ERK1/2 signal pathway. J Cell Biochem. 2012;113:2704–13.PubMedCentralPubMedCrossRef
56.
Milara J, Serrano A, Peiró T, Artigues E, Gavaldà A, Miralpeix M, Morcillo EJ, Cortijo J. Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition. Eur Respir J. 2013;41:1264–74.PubMedCrossRef
57.
Asano K, Shikama Y, Shibuya Y, Nakajima H, Kanai K, Yamada N, Suzaki H. Suppressive activity of tiotropium bromide on matrix metalloproteinase production from lung fibroblasts in vitro. Int J Chron Obstruct Pulmon Dis. 2008;3:781–9.PubMedCentralPubMed
58.
Haddad EB, Rousell J, Mak JC, Barnes PJ. Transforming growth factor-beta 1 induces transcriptional down-regulation of m2 muscarinic receptor gene expression. Mol Pharmacol. 1996;49:781–7.PubMed
59.
Haddad EB, Rousell J, Mak JC, Barnes PJ. Long-term carbachol treatment-induced down-regulation of muscarinic M2-receptors but not m2 receptor mRNA in a human lung cell line. Br J Pharmacol. 1995;116:2027–32.PubMedCentralPubMedCrossRef
60.
Matthiesen S, Bahulayan A, Kempkens S, Haag S, Fuhrmann M, Stichnote C, Juergens UR, Racké K. Muscarinic receptors mediate stimulation of human lung fibroblast proliferation. Am J Respir Cell Mol Biol. 2006;35:621–7.PubMedCrossRef
61.
Postma DS, Reddel HK, ten Hacken NH, van den Berge M. Asthma and chronic obstructive pulmonary disease: similarities and differences. Clin Chest Med. 2014;35:143–56.PubMedCrossRef
62.
Postma DS, Kerkhof M, Boezen HM, Koppelman GH. Asthma and chronic obstructive pulmonary disease: common genes, common environments? Am J Respir Crit Care Med. 2011;183:1588–94.PubMedCrossRef
63.
Meurs H, Oenema TA, Kistemaker LE, Gosens R. A new perspective on muscarinic receptor antagonism in obstructive airways diseases. Curr Opin Pharmacol. 2013;13:316–23.PubMedCrossRef
64.
Evans RA, Morgan MD. The systemic nature of chronic lung disease. Clin Chest Med. 2014;35:283–93.PubMedCrossRef
65.
Prakash YS. Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol. 2013;305(12):L912–33.PubMedCentralPubMedCrossRef
66.
Lammers JW, Minette P, McCusker M, Barnes PJ. The role of pirenzepine-sensitive (M1) muscarinic receptors in vagally mediated bronchoconstriction in humans. Am Rev Respir Dis. 1989;139:446–9.PubMedCrossRef
67.
Fryer AD, Jacoby DB. Muscarinic receptors and control of airway smooth muscle. Am J Respir Crit Care Med. 1998;158:S154–60.PubMedCrossRef
68.
Xiao H, Liao Z, Meng X, Yan X, Chen S, Mo Z. Effects of the selective muscarinic receptor antagonist penehyclidine hydrochloride on the respiratory tract. Pharmazie. 2009;64:337–41.PubMed
69.
Brown SM, Koarai A, Sturton RG, Nicholson AG, Barnes PJ, Donnelly LE. A role for M(2) and M(3) muscarinic receptors in the contraction of rat and human small airways. Eur J Pharmacol. 2013;702:109–15.PubMedCrossRef
70.
Castro JM, Resende RR, Mirotti L, Florsheim E, Albuquerque LL, Lino-dos-Santos-Franco A, Gomes E, de Lima WT, de Franco M, Ribeiro OG, Russo M. Role of m2 muscarinic receptor in the airway response to methacholine of mice selected for minimal or maximal acute inflammatory response. Biomed Res Int. 2013;2013:805627.PubMedCentralPubMed
71.
Rynko AE, Fryer AD, Jacoby DB. Interleukin-1β mediates virus-induced M2 muscarinic receptor dysfunction and airway hyperreactivity. Am J Respir Cell Mol Biol. 2014;51(4):494-501
72.
Roffel AF, Elzinga CR, Zaagsma J. Muscarinic M3 receptors mediate contraction of human central and peripheral airway smooth muscle. Pulm Pharmacol. 1990;3:47–51.PubMedCrossRef
73.
Cao R, Dong XW, Jiang JX, Yan XF, He JS, Deng YM, Li FF, Bao MJ, Xie YC, Chen XP, Xie QM. M(3) muscarinic receptor antagonist bencycloquidium bromide attenuates allergic airway inflammation, hyperresponsiveness and remodeling in mice. Eur J Pharmacol. 2011;655:83–90.PubMedCrossRef
74.
Kong KC, Billington CK, Gandhi U, Panettieri RA Jr, Penn RB. Cooperative mitogenic signaling by G protein-coupled receptors and growth factors is dependent on G(q/11). FASEB J. 2006;20:1558–60.PubMedCrossRef
75.
Oenema TA, Smit M, Smedinga L, Racké K, Halayko AJ, Meurs H, Gosens R. Muscarinic receptor stimulation augments TGF-β1-induced contractile protein expression by airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2012;303:L589–97.PubMedCrossRef
76.
Gosens R, Bos IS, Zaagsma J, Meurs H. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am J Respir Crit Care Med. 2005;171:1096–102.PubMedCrossRef
77.
Bos IS, Gosens R, Zuidhof AB, Schaafsma D, Halayko AJ, Meurs H, Zaagsma J. Inhibition of allergen-induced airway remodeling by tiotropium and budesonide: a comparison. Eur Respir J. 2007;30:653–61.PubMedCrossRef
Metadaten
Titel
Airway and Lung Remodelling in Chronic Pulmonary Obstructive Disease: A Role for Muscarinic Receptor Antagonists?
verfasst von
Michael Roth
Publikationsdatum
01.01.2015
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 1/2015
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-014-0319-0

Weitere Artikel der Ausgabe 1/2015

Drugs 1/2015 Zur Ausgabe

Erratum

Erratum to: Empagliflozin: A Review of Its Use in Patients with Type 2 Diabetes Mellitus

Review Article

Pharmacodynamics, Efficacy and Safety of Sodium–Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus

Adis Drug Evaluation

Umeclidinium/Vilanterol: A Review of Its Use as Maintenance Therapy in Adults with Chronic Obstructive Pulmonary Disease

Adis Drug Evaluation

Alectinib: A Review of Its Use in Advanced ALK-Rearranged Non-Small Cell Lung Cancer

Adis Drug Evaluation

Delamanid: A Review of Its Use in Patients with Multidrug-Resistant Tuberculosis

Adis Drug Evaluation

Dextromethorphan/Quinidine: A Review of Its Use in Adults with Pseudobulbar Affect