DOI QR코드

DOI QR Code

Recent Advances in the Development of Novel Drug Candidates for Regulating the Secretion of Pulmonary Mucus

  • Li, Xin (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Jin, Fengri (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Lee, Hyun Jae (Smith Liberal Arts College and Department of Addiction Science, Graduate School, Sahmyook University) ;
  • Lee, Choong Jae (Department of Pharmacology, School of Medicine, Chungnam National University)
  • Received : 2020.01.01
  • Accepted : 2020.02.17
  • Published : 2020.07.01

Abstract

Hypersecretion of pulmonary mucus is a major pathophysiological feature in allergic and inflammatory respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). Overproduction and/or oversecretion of mucus cause the airway obstruction and the colonization of pathogenic microbes. Developing a novel pharmacological agent to regulate the production and/or secretion of pulmonary mucus can be a useful strategy for the effective management of pathologic hypersecretion of mucus observed in COPD and asthma. Thus, in the present review, we tried to give an overview of the conventional pharmacotherapy for mucus-hypersecretory diseases and recent research results on searching for the novel candidate agents for controlling of pulmonary mucus hypersecretion, aiming to shed light on the potential efficacious pharmacotherapy of mucus-hypersecretory diseases.

Keywords

References

  1. Advenier, C., Lagente, V. and Boichot, E. (1997) The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough. Eur. Respir. J. 10, 1892-1906. https://doi.org/10.1183/09031936.97.10081892
  2. Aggarwal, S., Kim, S. W., Cheon, K., Tabassam, F. H., Yoon, J. H. and Koo, J. S. (2006) Nonclassical action of retinoic acid on the activation of the cAMP response element-binding protein in normal human bronchial epithelial cells. Mol. Biol. Cell 17, 566-575. https://doi.org/10.1091/mbc.E05-06-0519
  3. Albers, G. M., Tomkiewicz, R. P., May, M. K., Ramirez, O. E. and Rubin, B. K. (1996) Ring distraction technique for measuring surface tension of sputum: relationship to sputum clearability. J. Appl. Physiol. 81, 2690-2695. https://doi.org/10.1152/jappl.1996.81.6.2690
  4. Allegra, L., Bossi, R. and Braga, P. C. (1981) Action of sobrerol on mucociliary transport. Respiration 42, 105-109. https://doi.org/10.1159/000194412
  5. Barnes, P. J. (1998) Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin. Sci. 94, 557-572. https://doi.org/10.1042/cs0940557
  6. Bennett, W. D., Henderson, A. G. and Donaldson, S. H. (2016) Hydrator therapies for chronic bronchitis: lessons from cystic fibrosis. Ann. Am. Thorac. Soc. 13, 186-190.
  7. Bertrand, C. and Geppetti, P. (1996) Tachykinin and kinin receptor antagonists: therapeutic perspectives in allergic airway disease. Trends Pharmacol. Sci. 17, 255-259. https://doi.org/10.1016/0165-6147(96)10027-4
  8. Bilton, D., Tino, G., Barker, A. F., Chambers, D. C., De Soyza, A., Dupont, L. J., O’Dochartaigh, C., van Haren, E. H., Vidal, L. O., Welte, T., Fox, H. G., Wu, J. and Charlton, B. (2014) Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial. Thorax 69, 1073-1079. https://doi.org/10.1136/thoraxjnl-2014-205587
  9. British Thoracic Society Research Committee (1985) Oral N-acetylcysteine and exacerbation rates in patients with chronic bronchitis and severe airways obstruction. Thorax 40, 832-835. https://doi.org/10.1136/thx.40.11.832
  10. Chang, J. H., Song, K. J., Kim, H. J., Kim, J. H., Kim, N. H. and Kim, K. S. (2010) Dietary polyphenols affect MUC5AC expression and ciliary movement in respiratory cells and nasal mucosa. Am. J. Rhinol. Allergy 24, e59-e62. https://doi.org/10.2500/ajra.2010.24.3447
  11. Chen, Y., Watson, A. M., Williamson, C. D., Rahimi, M., Liang, C., Colberg- Poley, A. M. and Rose, M. C. (2012) Glucocorticoid receptor and HDAC2 mediate dexamethasone-induced repression of MUC5AC gene expression. Am. J. Respir. Cell Mol. Biol. 47, 637-644. https://doi.org/10.1165/rcmb.2012-0009OC
  12. Cho, K., Lee, H. J., Lee, S. Y., Woo, H., Lee, M. N., Seok, J. H. and Lee, C. J. (2011) Oleanolic acid and ursolic acid derived from Cornus officinalis Sieb. et Zucc. suppress epidermal growth factor- and phorbol ester-induced MUC5AC mucin production and gene expression from human airway epithelial cells. Phytother. Res. 25, 760-764. https://doi.org/10.1002/ptr.3488
  13. Choi, B. S., Kim, Y. J., Choi, J. S., Lee, H. J. and Lee, C. J. (2019) Obtusifolin isolated from the seeds of Cassia obtusifolia regulates the gene expression and production of MUC5AC mucin in airway epithelial cells via affecting NF-$\kappa$B pathway. Phytother. Res. 33, 919-928. https://doi.org/10.1002/ptr.6284
  14. Choi, B. S., Kim, Y. J., Yoon, Y. P., Lee, H. J. and Lee, C. J. (2018) Tussilagone suppressed the production and gene expression of MUC5AC mucin via regulating nuclear factor-kappa B signaling pathway in airway epithelial cells. Korean J. Physiol. Pharmacol. 22, 671-677. https://doi.org/10.4196/kjpp.2018.22.6.671
  15. Choi, J. H., Hwang, Y. P., Han, E. H., Kim, H. G., Park, B. H., Lee, H. S., Park, B. K., Lee, Y. C., Chung, Y. C. and Jeong, H. G. (2011) Inhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorum root-derived saponin in A549 cells. Food Chem. Toxicol. 49, 2157-2166. https://doi.org/10.1016/j.fct.2011.05.030
  16. Davis, C. W. (2002) Regulation of mucin secretion from in vitro cellular models. Novartis Found. Symp. 248, 113-125.
  17. Decramer, M., Rutten-van, Molken M., Dekhuijzen, P. N., Troosters, T., van Herwaarden, C. and Pellegrino, R. (2005) Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomized placebo-controlled trial. Lancet 365, 1552-1560. https://doi.org/10.1016/S0140-6736(05)66456-2
  18. Desaki, M., Tazikawa, H., Ohtoshi, T., Kasama, T., Kobayashi, K., Sunazuka, T., Omura, S., Yamamoto, K. and Ito, K. (2000) Erythromycin suppresses nuclear factor-kappaB and activator protein-1 activation in human bronchial epithelial cells. Biochem. Biophys. Res. Commun. 267, 124-128. https://doi.org/10.1006/bbrc.1999.1917
  19. Germouty, J. and Jirou-Najou, J. L. (1987) Clinical efficacy of ambroxol in the treatment of bronchial stasis: clinical trial in 120 patients at two different doses. Respiration 51, 37-41. https://doi.org/10.1159/000195273
  20. Green, T. D, Crews, A. L., Park, J., Fang, S. and Adler, K. B. (2011) Regulation of mucin secretion and inflammation in asthma: a role for MARCKS protein? Biochim. Biophys. Acta 1810, 1110-1113. https://doi.org/10.1016/j.bbagen.2011.01.009
  21. Guo, R., Canter, P. H. and Ernst, E. (2006) Herbal medicines for the treatment of rhinosinusitis: a systematic review. Otolaryngol. Head Neck Surg. 135, 496-506. https://doi.org/10.1016/j.otohns.2006.06.1254
  22. Guyatt, G. H., Townsend, M., Kazim, F. and Newhouse, M. T. (1987) A controlled trial of ambroxol in chronic bronchitis. Chest 92, 618-620. https://doi.org/10.1378/chest.92.4.618
  23. Hansen, N. C., Skriver, A., Brorsen-Riis, L., Balslov, S., Evald, T. and Maltbaek, N. (1994) Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis. Respir. Med. 88, 531-535. https://doi.org/10.1016/S0954-6111(05)80337-3
  24. Hauber, H. P., Bergeron, C., Tsicopoulos, A., Wallaert, B., Olivenstein, R., Holroyd, K. J., Levitt, R. C. and Hamid, Q. (2005a) Increased expression of the calcium-activated chloride channel hCLCA1 in airways of patients with obstructive chronic bronchitis. Can. Respir. J. 12, 143-146. https://doi.org/10.1155/2005/531432
  25. Hauber, H. P., Daigneault, P., Frenkiel, S., Lavigne, F., Hung, H. L., Levitt, R. C. and Hamid, Q. (2005b) Niflumic acid and MSI-2216 reduce TNF-alpha-induced mucin expression in human airway mucosa. J. Allergy Clin. Immunol. 115, 266-271. https://doi.org/10.1016/j.jaci.2004.09.039
  26. Hauber, H. P., Tsicopoulos, A., Wallaert, B., Griffin, S., McElvaney, N. G., Daigneault, P., Mueller, Z., Olivenstein, R., Holroyd, K. J., Levitt, R. C. and Hamid, Q. (2004) Expression of HCLCA1 in cystic fibrosis lungs is associated with mucus overproduction. Eur. Respir. J. 23, 846-850. https://doi.org/10.1183/09031936.04.00096504
  27. Hauber, H. P., Goldmann, T., Vollmer, E., Wollenberg, B., Hung, H. L., Levitt, R. C. and Zabel, P. (2007b) LPS-induced mucin expression in human sinus mucosa can be attenuated by hCLCA inhibitors. J. Endotoxin Res. 13, 109-116. https://doi.org/10.1177/0968051907079168
  28. Hauber, H. P., Goldmann, T., Vollmer, E., Wollenberg, B. and Zabel, P. (2007a) Effect of dexamethasone and ACC on bacteria-induced mucin expression in human airway mucosa. Am. J. Respir. Cell Mol. Biol. 37, 606-616. https://doi.org/10.1165/rcmb.2006-0404OC
  29. Henke, M. O. and Ratjen, F. (2007) Mucolytics in cystic fibrosis. Paediatr. Respir. Rev. 8, 24-29. https://doi.org/10.1016/j.prrv.2007.02.009
  30. Henke, M. O., Renner, A., Huber, R. M., Seeds, M. C. and Rubin, B. K. (2004) MUC5AC and MUC5B mucins are decreased in cystic fibrosis airway secretions. Am. J. Respir. Cell Mol. Biol. 31, 86-91. https://doi.org/10.1165/rcmb.2003-0345OC
  31. Henke, M. O., John, G., Germann, M., Lindemann, H. and Rubin, B. K. (2007) MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation. Am. J. Respir. Crit. Care Med. 175, 816-821. https://doi.org/10.1164/rccm.200607-1011OC
  32. Heo, H. J., Kim, C., Lee, H. J., Kim, Y. S., Kang, S. S., Seo, U. K., Kim, Y. H., Park, Y. C., Seok, J. H. and Lee, C. J. (2007b) Carbenoxolone and triterpenoids inhibited mucin secretion from airway epithelial cells. Phytother. Res. 21, 462-465. https://doi.org/10.1002/ptr.2102
  33. Heo, H. J., Lee, H. J., Kim, Y. S., Kang, S. S., Son, K. H., Seok, J. H., Seo, U. K. and Lee, C. J. (2007a) Effects of baicalin and wogonin on mucin release from cultured airway epithelial cells. Phytother. Res. 21, 1130-1134. https://doi.org/10.1002/ptr.2222
  34. Heo, H. J., Lee, S. Y., Lee, M. N., Lee, H. J., Seok, J. H. and Lee, C. J. (2009) Genistein and curcumin suppress epidermal growth factor-induced MUC5AC mucin production and gene expression from human airway epithelial cells. Phytother. Res. 23, 1458-1461. https://doi.org/10.1002/ptr.2801
  35. Hoshino, M., Morita, S., Iwashita, H., Sagiya, Y., Nagi, T., Nakanishi, A., Ashida, Y., Nishimura, O., Fujisawa, Y. and Fujino, M. (2002) Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway. Am. J. Respir. Crit. Care Med. 165, 1132-1136. https://doi.org/10.1164/ajrccm.165.8.2107068
  36. Jager, E. G. (1989) Double-blind, placebo-controlled clinical evaluation of guaimesal in outpatients. Clin. Ther. 11, 341-362.
  37. Jiang, D.-P., Perelman, J. M., Kolosov, V. P. and Zhou, X.-D. (2011) Effects of scutellarin on MUC5AC mucin production induced by human neutrophil elastase or interleukin-13 on airway epithelial cells. J. Korean Med. Sci. 26, 778-784. https://doi.org/10.3346/jkms.2011.26.6.778
  38. Joos, G. F., Kips, J. C., Peleman, R. A. and Pauwels, R. A. (1995) Tachykinin antagonists and the airways. Arch. Int. Pharmacodyn. Ther. 329, 205-219.
  39. Kater, A., Henke, M. O. and Rubin, B. K. (2007) The role of DNA and actin polymers on the polymer structure and rheology of cystic fibrosis sputum and depolymerization by gelsolin or thymosin beta 4. Ann. N. Y. Acad. Sci. 1112, 140-153. https://doi.org/10.1196/annals.1415.006
  40. Kim, E. J., Yoon, Y. P., Woo, K. W., Kim, J. H., Min, S. Y., Lee, H. J., Lee, S. K., Hong, J. H., Lee, K. R. and Lee, C. J. (2016) Verticine, ebeiedine and suchengbeisine isolated from the bulbs of Fritillaria thunbergii Miq. inhibited the gene expression and production of MUC5AC mucin from human airway epithelial cells. Phytomedicine 23, 95-104. https://doi.org/10.1016/j.phymed.2015.12.016
  41. Kim, J. H., Chang, J. H., Yoon, J. H., Kwon, S. H., Bae, J. H. and Kim, K. S. (2009) 6-Gingerol supresses interleukin-1beta-induced MUC5AC gene expression in human airway epithelial cells. Am. J. Rhinol. Allergy 23, 385-391. https://doi.org/10.2500/ajra.2009.23.3337
  42. Kim, J. O., Sikder, M. A., Lee, H. J., Rahman, M., Kim, J. H., Chang, G. T. and Lee, C. J. (2012a) Phorbol ester or epidermal growth-factorinduced MUC5AC mucin gene expression and production from airway epithelial cells are inhibited by apigenin and wogonin. Phytother. Res. 26, 1784-1788. https://doi.org/10.1002/ptr.4650
  43. Kim, K. D., Lee, H. J., Lim, S. P., Sikder, M. A., Lee, S. Y. and Lee, C. J. (2012b) Silibinin regulates gene expression, production and secretion of mucin from cultured airway epithelial cells. Phytother. Res. 26, 1301-1307. https://doi.org/10.1002/ptr.3727
  44. Koo, J. S., Jetten, A. M., Belloni, P., Yoon, J. H., Kim, Y. D. and Nettesheim, P. (1999) Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells. Biochem. J. 338, 351-357. https://doi.org/10.1042/bj3380351
  45. Kwon, S. H., Nam, J. I., Kim, S. H., Kim, J. H., Yoon, J. H. and Kim, K. S. (2009) Kaempferol and quercetin, essential ingredients in Ginkgo biloba extract, inhibit interleukin-1$\beta$-induced MUC5AC gene expression in human airway epithelial cells. Phytother. Res. 23, 1708-1712. https://doi.org/10.1002/ptr.2817
  46. Lasker, J. M., Chen, W. B., Wolf, I., Bloswick, B. P., Wilson, P. D. and Powell, P. K. (2000) Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J. Biol. Chem. 275, 4118-4126. https://doi.org/10.1074/jbc.275.6.4118
  47. Lee, C. J., Lee, J. H., Seok, J. H., Hur, G. M., Park, J. s., Bae, S., Lim, J. H., and Park, Y. C. (2004a) Effects of betaine, coumarin and flavonoids on mucin release from cultured hamster tracheal surface epithelial cells. Phytother. Res. 18, 301-305. https://doi.org/10.1002/ptr.1433
  48. Lee, C. J., Lee, J. H., Seok, J. H., Hur, G. M., Park, Y. C., Seol, I. C. and Kim, Y. H. (2003) Effects of baicalein, berberine, curcumin and hesperidin on mucin release from airway goblet cells. Planta Med. 69, 523-526. https://doi.org/10.1055/s-2003-40655
  49. Lee, C. J., Seok, J. H., Hur, G. M., Lee, J. H., Park, J. S., Seol, I. C. and Kim, Y. H. (2004b) Effects of ursolic acid, betulin and sulfur- containing compounds on mucin release from airway goblet cells. Planta Med. 70, 1119-1122. https://doi.org/10.1055/s-2004-835837
  50. Lee, H. J., Lee, S. Y., Bae, H. S., Kim, J. H., Chang, G. T., Seok, J. H. and Lee, C. J. (2011a) Inhibition of airway MUC5AC mucin production and gene expression induced by epidermal growth factor or phorbol ester by glycyrrhizin and carbenoxolone. Phytomedicine 18, 743-747. https://doi.org/10.1016/j.phymed.2010.11.003
  51. Lee, H. J., Lee, S. Y., Lee, M. N., Kim, J. H., Chang, G. T., Seok, J. H. and Lee, C. J. (2011b) Inhibition of secretion, production and gene expression of mucin from cultured airway epithelial cells by prunetin. Phytother. Res. 25, 1196-1200. https://doi.org/10.1002/ptr.3362
  52. Lee, H. J., Lee, S. Y., Lee, M. N., Kim, J. H., Chang, G. T., Seok, J. H. and Lee, C. J. (2011c) Daidzein regulates secretion, production and gene expression of mucin from airway epithelial cells stimulated by proinflammatory factor and growth factor. Pulm. Pharmacol. Ther. 24, 128-132. https://doi.org/10.1016/j.pupt.2010.08.003
  53. Lee, H. J., Park, J. S., Yoon, Y. P., Shin, Y. J., Lee, S. K., Kim, Y. S., Hong, J. H., Son, K. H. and Lee, C. J. (2015a) Dioscin and methylprotodioscin isolated from the root of Asparagus cochinchinensis suppressed the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor. Phytomedicine 22, 568-572. https://doi.org/10.1016/j.phymed.2015.03.009
  54. Lee, H. J., Ryu, J., Park, S. H., Seo, E. K., Han, A. R., Lee, S. K., Kim, Y. S., Hong, J. H., Seok, J. H. and Lee, C. J. (2015b) Suppressive effects of coixol, glyceryl trilinoleate and natural products derived from Coix Lachryma-Jobi var. ma-yuen on gene expression, production and secretion of airway MUC5AC mucin. Arch. Pharm. Res. 38, 620-627. https://doi.org/10.1007/s12272-014-0377-6
  55. Lee, H. J., Ryu, J., Park, S. H., Woo, E. R., Kim, A. R., Lee, S. K., Kim, Y. S., Kim, J. O., Hong, J. H. and Lee, C. J. (2014) Effects of Morus alba L. and natural products including morusin on in vivo secretion and in vitro production of airway MUC5AC mucin. Tuberc. Respir. Dis. (Seoul) 77, 65-72. https://doi.org/10.4046/trd.2014.77.2.65
  56. Lee, H. J., Seo, H. S., Ryu, J., Yoon, Y. P., Park, S. H. and Lee, C. J. (2015c) Luteolin inhibited the gene expression, production and secretion of MUC5AC mucin via regulation of nuclear factor kappa B signaling pathway in human airway epithelial cells. Pulm. Pharmacol. Ther. 31, 117-122. https://doi.org/10.1016/j.pupt.2014.09.008
  57. Lee, S. U., Sung, M. H., Ryu, H. W., Lee, J., Kim, H. S., In, H. J., Ahn, K. S., Lee, H. J., Lee, H. K., Shin, D. H., Lee, Y., Hong, S. T. and Oh, S. R. (2015d) Verproside inhibits TNF-$\alpha$-induced MUC5AC expression through suppression of the TNF-$\alpha$/NF-$\kappa$B pathway in human airway epithelial cells. Cytokine 77, 168-175. https://doi.org/10.1016/j.cyto.2015.08.262
  58. Lee, S. Y., Lee, H. J., Sikder, M. A., Shin, H. D., Kim, J. H., Chang, G. T., Seok, J. H. and Lee, C. J. (2012) Resveratrol inhibits mucin gene expression, production and secretion from airway epithelial cells. Phytother. Res. 26, 1082-1087. https://doi.org/10.1002/ptr.3701
  59. Li, Y., Martin, L. D., Spizz, G. and Adler, K. B. (2001) MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro. J. Biol. Chem. 276, 40982-40990. https://doi.org/10.1074/jbc.M105614200
  60. Matthys, H., de Mey, C., Carls, C., Rys, A., Geib, A. and Wittig, T. (2000) Efficacy and tolerability of myrtol standardized in acute bronchitis. A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol. Arzneimittelforschung 50, 700-711. https://doi.org/10.1055/s-0031-1300276
  61. Nakanishi, A., Morita, S., Iwashita, H., Sagiya, Y., Ashida, Y., Shirafuji, H., Fujisawa, Y., Nishimura, O. and Fujino, M. (2001) Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma. Proc. Natl. Acad. Sci. U.S.A. 98, 5175-5180. https://doi.org/10.1073/pnas.081510898
  62. Nie, Y. C., Wu, H., Li, P. B., Xie, L. M., Luo, Y. L., Shen, J. G. and Su, W. W. (2012) Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-I$\kappa$B-NF-$\kappa$B signaling pathways. Eur. J. Pharmacol. 690, 207-213. https://doi.org/10.1016/j.ejphar.2012.06.040
  63. Nishimoto, Y., Hisatsune, A., Katsuki, H., Miyata, T., Yokomizo, K. and Isohama, Y. (2010) Glycyrrhizin attenuates mucus production by inhibition of MUC5AC mRNA expression in vivo and in vitro. J. Pharmacol. Sci. 113, 76-83. https://doi.org/10.1254/jphs.09344FP
  64. No authors listed (1989) Prevention of chronic bronchitis exacerbations with ambroxol (mucosolvan retard). An open, long-term, multicenter study in 5,635 patients. Respiration 55, 84-96.
  65. Ou, X. M., Feng, Y. L., Wen, F. Q., Wang, K., Yang, J., Deng, Z. P., Liu, D. S. and Li, Y. P. (2008) Macrolides attenuate mucus hypersecretion in rat airways through inactivation of NF-kappaB. Respirology 13, 63-72. https://doi.org/10.1111/j.1440-1843.2007.01213.x
  66. Park, J. W., Shin, N. R., Shin, I. S., Kwon, O. K., Kim, J. S., Oh, S. R., Kim, J. H. and Ahn, K. S. (2016) Silibinin inhibits neutrophilic inflammation and mucus secretion induced by cigarette smoke via suppression of ERK-SP1 pathway. Phytother. Res. 30, 1926-1936. https://doi.org/10.1002/ptr.5686
  67. Park, S. H., Lee, H. J., Ryu, J., Son, K. H., Kwon, S. Y., Lee, S. K., Kim, Y. S., Hong, J. H., Seok, J. H. and Lee, C. J. (2014) Effects of ophiopogonin D and spicatoside A derived from Liriope Tuber on secretion and production of mucin from airway epithelial cells. Phytomedicine 21, 172-176. https://doi.org/10.1016/j.phymed.2013.08.013
  68. Rogers, D. F. (2007) Mucoactive agents for airway mucus hypersecretory diseases. Respir. Care 52, 1176-1193.
  69. Rogers, D. F. and Barnes, P. J. (2006) Treatment of airway mucus hypersecretion. Ann. Med. 38, 116-125. https://doi.org/10.1080/07853890600585795
  70. Rubin, B. K. (1999) Who will benefit from DNase? Pediatr. Pulmonol. 27, 3-4. https://doi.org/10.1002/(SICI)1099-0496(199901)27:1<3::AID-PPUL2>3.0.CO;2-A
  71. Rubin, B. K., Kater, A. P. and Goldstein, A. L. (2006) Thymosin b4 sequesters actin in cystic fibrosis sputum and decreases sputum cohesivity in vitro. Chest 130, 1433-1440. https://doi.org/10.1016/s0012-3692(15)37320-7
  72. Rubin, B. K., Ramirez, O. and Ohar, J. A. (1996) Iodinated glycerol has no effect on pulmonary function, symptom score, or sputum properties in patients with stable chronic bronchitis. Chest 109, 348-352. https://doi.org/10.1378/chest.109.2.348
  73. Ryu, J., Lee, H. J., Park, S. H., Kim, J., Lee, D., Lee, S. K., Kim, Y. S., Hong, J. H., Seok, J. H. and Lee, C. J. (2014) Effects of the root of Platycodon grandiflorum on airway mucin hypersecretion in vivo and platycodin D(3) and deapi-platycodin on production and secretion of airway mucin in vitro. Phytomedicine 21, 529-533. https://doi.org/10.1016/j.phymed.2013.10.004
  74. Ryu, J., Lee, H. J., Park, S. H., Sikder, M. A., Kim, J. O., Hong, J. H., Seok, J. H. and Lee, C. J. (2013) Effect of prunetin on TNF-$\alpha$-induced MUC5AC mucin gene expression, production, degradation of I$\kappa$B and translocation of NF-$\kappa$B p65 in human airway epithelial cells. Tuberc. Respir. Dis. (Seoul) 75, 205-209. https://doi.org/10.4046/trd.2013.75.5.205
  75. Seo, H. S., Sikder, M. A., Lee, H. J., Ryu, J. and Lee, C. J. (2014) Apigenin inhibits tumor necrosis factor-$\alpha$-induced production and gene expression of mucin through regulating nuclear factor-kappa B signaling pathway in airway epithelial cells. Biomol. Ther. (Seoul) 22, 525-531. https://doi.org/10.4062/biomolther.2014.094
  76. Sheffner, A. L., Medler, E. M., Jacobs, L. W. and Sarett, H. P. (1964) The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am. Rev. Respir. Dis. 90, 721-729.
  77. Shim, C., King, M. and Williams, M. H., Jr. (1987) Lack of effect of hydration on sputum production in chronic bronchitis. Chest 92, 679-682. https://doi.org/10.1378/chest.92.4.679
  78. Shimizu, T., Shimizu, S., Hattori, R., Gabazza, E. C. and Majima, Y. (2003) In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells. Am. J. Respir. Crit. Care Med. 168, 581-587. https://doi.org/10.1164/rccm.200212-1437OC
  79. Shin, C. Y., Lee, W. J., Lee, E. B., Choi, E. Y. and Ko, K. H. (2002) Platycodin D and D3 increase airway mucin release in vivo and in vitro in rats and hamsters. Planta Med. 68, 221-225. https://doi.org/10.1055/s-2002-23130
  80. Shin, H. D., Lee, H. J., Sikder, M. A., Park, S. H., Ryu, J., Hong, J. H., Kim, J. O., Seok, J. H. and Lee, C. J. (2012) Effect of chrysin on gene expression and production of MUC5AC mucin from cultured airway epithelial cells. Tuberc. Respir. Dis. (Seoul) 73, 204-209. https://doi.org/10.4046/trd.2012.73.4.204
  81. Sikder, M. A., Lee, H. J., Lee, S. Y., Bae, H. S., Kim, J. H., Chang, G. T. and Lee, C. J. (2011) Effect of berberine on MUC5AC mucin gene expression and mucin production from human airway epithelial cells. Biomol. Ther. (Seoul) 19, 320-323. https://doi.org/10.4062/biomolther.2011.19.3.320
  82. Sikder, M. A., Lee, H. J., Mia, M. Z., Park, S. H., Ryu, J., Kim, J. H., Min, S. Y., Hong, J. H., Seok, J. H. and Lee, C. J. (2014a) Inhibition of TNF-$\alpha$-induced MUC5AC mucin gene expression and production by wogonin through the inactivation of NF-$\kappa$B signaling in airway epithelial cells. Phytother. Res. 28, 62-68. https://doi.org/10.1002/ptr.4954
  83. Sikder, M. A., Lee, H. J., Ryu, J., Park, S. H., Kim, J. O., Hong, J. H., Seok, J. H. and Lee, C. J. (2014b) Apigenin and wogonin regulate epidermal growth factor receptor signaling pathway involved in MUC5AC mucin gene expression and production from cultured airway epithelial cells. Tuberc. Respir. Dis. (Seoul) 76, 120-126. https://doi.org/10.4046/trd.2014.76.3.120
  84. Singer, M., Martin, L. D., Vargaftig, B. B., Park, J., Gruber, A. D., Li, Y. and Adler, K. B. (2004) A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nat. Med. 10, 193-196. https://doi.org/10.1038/nm983
  85. Song, W. Y., Song, Y. S., Ryu, H. W., Oh, S. R., Hong, J. and Yoon, D. Y. (2017) Tilianin inhibits MUC5AC expression mediated via downregulation of EGFR-MEK-ERK-Sp1 signaling pathway in NCIH292 human airway cells. J. Microbiol. Biotechnol. 27, 49-56. https://doi.org/10.4014/jmb.1610.10012
  86. Tamaoki, J. (2004) The effects of macrolides on inflammatory cells. Chest 125, 41-50. https://doi.org/10.1378/chest.125.2_suppl.41S
  87. Tamaoki, J., Takeyama, K., Tagaya, E. and Konno, K. (1995) Effect of clarithromycin on sputum production and its rheological properties in chronic respiratory tract infections. Antimicrob. Agents Chemother. 39, 1688-1690. https://doi.org/10.1128/AAC.39.8.1688
  88. Toda, M., Tulic, M. K., Levitt, R. C. and Hamid, Q. J. (2002) A calciumactivated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma. J. Allergy Clin. Immunol. 109, 246-250. https://doi.org/10.1067/mai.2002.121555
  89. Valderramas, S. R. and Atallah, A. N. (2009) Effectiveness and safety of hypertonic saline inhalation combined with exercise training in patients with chronic obstructive pulmonary disease: a randomized trial. Respir. Care 54, 327-333.
  90. Vasconcellos, C. A., Allen, P. G., Wohl, M. E., Drazen, J. M., Janmey, P. A. and Stossel, T. P. (1994) Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Science 263, 969-971. https://doi.org/10.1126/science.8310295
  91. Voynow, J. A. and Rubin, B. K. (2009) Mucins, mucus, and sputum. Chest 135, 505-512. https://doi.org/10.1378/chest.08-0412
  92. Wang, T., Liu, Y., Chen, L., Wang, X., Hu, X. R., Feng, Y. L., Liu, D. S., Xu, D., Duan, Y. P., Lin, J., Ou, X. M. and Wen, F. Q. (2009) Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. Eur. Respir. J. 33, 1122-1132. https://doi.org/10.1183/09031936.00055908
  93. Wojtczak, H. A., Kerby, G. S., Wagener, J. S., Copenhaver, S. C., Gotlin, R. W., Riches, D. W. H. and Accurso, F. J. (2001) Beclomethasone diproprionate reduced airway inflammation without adrenal suppression in young children with cystic fibrosis: a pilot study. Pediatr. Pulmonol. 32, 293-302. https://doi.org/10.1002/ppul.1122
  94. Yang, T., Luo, F., Shen, Y., An, J., Li, X., Liu, X., Ying, B., Liao, Z., Dong, J., Guo, L., Wang, T., Xu, D., Chen, L. and Wen, F. (2012) Quercetin attenuates airway inflammation and mucus production induced by cigarette smoke in rats. Int. Immunopharmacol. 13, 73-81. https://doi.org/10.1016/j.intimp.2012.03.006
  95. Yoon, Y. P., Lee, H. J., Lee, D. U., Lee, S. K., Hong, J. H. and Lee, C. J. (2015) Effects of Lupenone, Lupeol, and Taraxerol Derived from Adenophora triphylla on the Gene Expression and Production of Airway MUC5AC Mucin. Tuberc. Respir. Dis. (Seoul) 78, 210-217. https://doi.org/10.4046/trd.2015.78.3.210
  96. Yoon, Y. P., Ryu, J., Park, S. H., Lee, H. J., Lee, S., Lee, S. K., Kim, J. O., Hong, J. H., Seok, J. H. and Lee, C. J. (2014) Effects of lobetyolin, lobetyol and methyl linoleate on secretion, production and gene expression of MUC5AC mucin from airway epithelial cells. Tuberc. Respir. Dis. (Seoul) 77, 203-208. https://doi.org/10.4046/trd.2014.77.5.203
  97. Zhou, Y., Shapiro, M., Dong, Q., Louahed, J., Weiss, C., Wan, S., Chen, Q., Dragwa, C., Savio, D., Huang, M., Fuller, C., Tomer, Y., Nicolaides, N. C., McLane, M. and Levitt, R. C. (2002) A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction. Novartis Found. Symp. 248, 150.
  98. Zhou, Z., Yang, N., Emala, C. and Li, X. M. (2015) The flavonoid 7,4′-dihydroxyflavone inhibits MUC5AC gene expression, production, and secretion via regulation of NF-$\kappa$B, STAT6, and HDAC2. Phytother. Res. 29, 925-932. https://doi.org/10.1002/ptr.5334

Cited by

  1. Diclofenac Inhibits Phorbol Ester-Induced Gene Expression and Production of MUC5AC Mucin via Affecting Degradation of IkBα and Translocation of NF-kB p65 in NCI-H292 Cells vol.28, pp.5, 2020, https://doi.org/10.4062/biomolther.2020.090
  2. Kaempferol Regulates the Expression of Airway MUC5AC Mucin Gene via IκBα-NF-κB p65 and p38-p44/42-Sp1 Signaling Pathways vol.29, pp.3, 2020, https://doi.org/10.4062/biomolther.2020.149
  3. Eriodictyol Inhibits the Production and Gene Expression of MUC5AC Mucin via the IκBα-NF-κB p65 Signaling Pathway in Airway Epithelial Cells vol.29, pp.6, 2021, https://doi.org/10.4062/biomolther.2021.091
  4. Investigation of the role of the autophagic protein LC3B in the regulation of human airway epithelium cell differentiation in COPD using a biomimetic model vol.13, 2020, https://doi.org/10.1016/j.mtbio.2021.100182