Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Mometasone Furoate Suppresses PMA-Induced MUC-5AC and MUC-2 Production in Human Airway Epithelial Cells

  • Received : 2015.10.05
  • Accepted : 2016.06.15
  • Published : 2017.01.31
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Abstract

Background: Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported. Methods: Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)-induction of mucin and TNF-${\alpha}$ in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1-500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone ($1{\mu}g/mL$) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-${\alpha}$ in culture supernatants were measured using enzyme-linked immunosorbent assay. Results: MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-${\alpha}$. Conclusion: Our findings demonstrated that MF and BUD attenuated mucin and TNF-${\alpha}$ production in PMA-induced human airway epithelial cells.

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References

  1. Zhang X, Morrison-Carpenter T, Holt JB, Callahan DB. Trends in adult current asthma prevalence and contributing risk factors in the United States by state: 2000-2009. BMC Public Health 2013;13:1156. https://doi.org/10.1186/1471-2458-13-1156
  2. Sedaghat AR, Phipatanakul W, Cunningham MJ. Prevalence of and associations with allergic rhinitis in children with chronic rhinosinusitis. Int J Pediatr Otorhinolaryngol 2014;78:343-7. https://doi.org/10.1016/j.ijporl.2013.12.006
  3. Mello JF Jr, Mion Ode G, Andrade NA, Anselmo-Lima WT, Stamm AE, Almeida WL, et al. Brazilian Academy of Rhinology position paper on topical intranasal therapy. Braz J Otorhinolaryngol 2013;79:391-400. https://doi.org/10.5935/1808-8694.20130067
  4. Yang D, Wang J, Bunjhoo H, Xiong W, Xu Y, Zhao J. Comparison of the efficacy and safety of mometasone furoate to other inhaled steroids for asthma: a meta-analysis. Asian Pac J Allergy Immunol 2013;31:26-35.
  5. Martinez-Anton A, Debolos C, Garrido M, Roca-Ferrer J, Barranco C, Alobid I, et al. Mucin genes have different expression patterns in healthy and diseased upper airway mucosa. Clin Exp Allergy 2006;36:448-57. https://doi.org/10.1111/j.1365-2222.2006.02451.x
  6. Kim DH, Chu HS, Lee JY, Hwang SJ, Lee SH, Lee HM. Up-regulation of MUC5AC and MUC5B mucin genes in chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg 2004;130:747-52.
  7. Morcillo EJ, Cortijo J. Mucus and MUC in asthma. Curr Opin Pulm Med 2006;12:1-6. https://doi.org/10.1097/01.mcp.0000198064.27586.37
  8. Kim YD, Kwon EJ, Park DW, Song SY, Yoon SK, Baek SH. Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Mol Pharmacol 2002;62:1112-8. https://doi.org/10.1124/mol.62.5.1112
  9. Takami S, Mizuno T, Oyanagi T, Tadaki H, Suzuki T, Muramatsu K, et al. Glucocorticoids inhibit MUC5AC production induced by transforming growth factor-alpha in human respiratory cells. Allergol Int 2012;61:451-9. https://doi.org/10.2332/allergolint.11-OA-0411
  10. Burgel PR, Cardell LO, Ueki IF, Nadel JA. Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps. Eur Respir J 2004;24:594-600. https://doi.org/10.1183/09031936.04.00014404
  11. Westergaard CG, Porsbjerg C, Backer V. A review of mometasone furoate/formoterol in the treatment of asthma. Expert Opin Pharmacother 2013;14:339-46. https://doi.org/10.1517/14656566.2013.761976
  12. Park SJ, Kim TH, Jun YJ, Lee SH, Ryu HY, Jung KJ, et al. Chronic rhinosinusitis with polyps and without polyps is associated with increased expression of suppressors of cytokine signaling 1 and 3. J Allergy Clin Immunol 2013;131:772-80. https://doi.org/10.1016/j.jaci.2012.12.671
  13. Brightling C, Berry M, Amrani Y. Targeting TNF-alpha: a novel therapeutic approach for asthma. J Allergy Clin Immunol 2008;121:5-10. https://doi.org/10.1016/j.jaci.2007.10.028
  14. Rudiger JJ, Gencay M, Yang JQ, Bihl M, Tamm M, Roth M. Fast beneficial systemic anti-inflammatory effects of inhaled budesonide and formoterol on circulating lymphocytes in asthma. Respirology 2013;18:840-7. https://doi.org/10.1111/resp.12104
  15. Ciprandi G, Tosca MA, Passalacqua G, Canonica GW. Intranasal mometasone furoate reduces late-phase inflammation after allergen challenge. Ann Allergy Asthma Immunol 2001;86:433-8. https://doi.org/10.1016/S1081-1206(10)62491-X
  16. Inoue D, Yamaya M, Kubo H, Sasaki T, Hosoda M, Numasaki M, et al. Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells. Respir Physiol Neurobiol 2006;154:484-99. https://doi.org/10.1016/j.resp.2005.11.006
  17. Li R, Meng Z. Effects of SO2 derivatives on expressions of MUC5AC and IL-13 in human bronchial epithelial cells. Arch Toxicol 2007;81:867-74. https://doi.org/10.1007/s00204-007-0212-7
  18. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25:402-8. https://doi.org/10.1006/meth.2001.1262
  19. Bamrungphon W, Prempracha N, Bunchu N, Rangdaeng S, Sandhu T, Srisukho S, et al. A new mucin antibody/enzymelinked lectin-sandwich assay of serum MUC5AC mucin for the diagnosis of cholangiocarcinoma. Cancer Lett 2007;247:301-8. https://doi.org/10.1016/j.canlet.2006.05.007
  20. Hewson CA, Edbrooke MR, Johnston SL. PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol 2004;344:683-95. https://doi.org/10.1016/j.jmb.2004.09.059
  21. Davies DE, Polosa R, Puddicombe SM, Richter A, Holgate ST. The epidermal growth factor receptor and its ligand family: their potential role in repair and remodelling in asthma. Allergy 1999;54:771-83.
  22. Shao MX, Nadel JA. Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci U S A 2005;102:767-72. https://doi.org/10.1073/pnas.0408932102
  23. Ishinaga H, Takeuchi K, Kishioka C, Suzuki S, Basbaum C, Majima Y. Pranlukast inhibits NF-kappaB activation and MUC2 gene expression in cultured human epithelial cells. Pharmacology 2005;73:89-96. https://doi.org/10.1159/000081294
  24. Bernstein DI, Berkowitz RB, Chervinsky P, Dvorin DJ, Finn AF, Gross GN, et al. Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler. Respir Med 1999;93:603-12. https://doi.org/10.1016/S0954-6111(99)90099-9
  25. Affrime MB, Cuss F, Padhi D, Wirth M, Pai S, Clement RP, et al. Bioavailability and metabolism of mometasone furoate following administration by metered-dose and dry-powder inhalers in healthy human volunteers. J Clin Pharmacol 2000;40:1227-36.
  26. Smith CL, Kreutner W. In vitro glucocorticoid receptor binding and transcriptional activation by topically active glucocorticoids. Arzneimittelforschung 1998;48:956-60.
  27. Valotis A, Hogger P. Significant receptor affinities of metabolites and a degradation product of mometasone furoate. Respir Res 2004;5:7. https://doi.org/10.1186/1465-9921-5-7
  28. Papi A, Papadopoulos NG, Degitz K, Holgate ST, Johnston SL. Corticosteroids inhibit rhinovirus-induced intercellular adhesion molecule-1 up-regulation and promoter activation on respiratory epithelial cells. J Allergy Clin Immunol 2000;105(2 Pt 1):318-26. https://doi.org/10.1016/S0091-6749(00)90082-4
  29. Sabatini F, Silvestri M, Sale R, Serpero L, Giuliani M, Scarso L, et al. Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling. Pulm Pharmacol Ther 2003;16:287-97. https://doi.org/10.1016/S1094-5539(03)00068-3
  30. Kim YD, Kwon EJ, Kwon TK, Baek SH, Song SY, Suh JS. Regulation of IL-1beta-mediated MUC2 gene in NCI-H292 human airway epithelial cells. Biochem Biophys Res Commun 2000;274:112-6. https://doi.org/10.1006/bbrc.2000.3107
  31. Feinstein MB, Schleimer RP. Regulation of the action of hydrocortisone in airway epithelial cells by 11beta-hydroxysteroid dehydrogenase. Am J Respir Cell Mol Biol 1999;21:403-8. https://doi.org/10.1165/ajrcmb.21.3.3560
  32. Chen Y, Nickola TJ, DiFronzo NL, Colberg-Poley AM, Rose MC. Dexamethasone-mediated repression of MUC5AC gene expression in human lung epithelial cells. Am J Respir Cell Mol Biol 2006;34:338-47. https://doi.org/10.1165/rcmb.2005-0176OC
  33. Barton BE, Jakway JP, Smith SR, Siegel MI. Cytokine inhibition by a novel steroid, mometasone furoate. Immunopharmacol Immunotoxicol 1991;13:251-61. https://doi.org/10.3109/08923979109019704
  34. Ek A, Larsson K, Siljerud S, Palmberg L. Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages. Allergy 1999;54:691-9. https://doi.org/10.1034/j.1398-9995.1999.00087.x
  35. Joyce DA, Kloda A, Steer JH. Dexamethasone suppresses release of soluble TNF receptors by human monocytes concurrently with TNF-alpha suppression. Immunol Cell Biol 1997;75:345-50. https://doi.org/10.1038/icb.1997.53
  36. Nakamura Y, Murai T, Ogawa Y. Effect of in vitro and in vivo administration of dexamethasone on rat macrophage functions: comparison between alveolar and peritoneal macrophages. Eur Respir J 1996;9:301-6. https://doi.org/10.1183/09031936.96.09020301
  37. Levine SJ, Larivee P, Logun C, Angus CW, Ognibene FP, Shelhamer JH. Tumor necrosis factor-alpha induces mucin hypersecretion and MUC-2 gene expression by human airway epithelial cells. Am J Respir Cell Mol Biol 1995;12:196-204. https://doi.org/10.1165/ajrcmb.12.2.7865217
  38. Ryu J, Lee HJ, Park SH, Sikder MA, Kim JO, Hong JH, et al. Effect of Prunetin on TNF-alpha-induced MUC5AC mucin gene expression, production, degradation of IkappaB and translocation of NF-kappaB p65 in human airway epithelial cells. Tuberc Respir Dis 2013;75:205-9. https://doi.org/10.4046/trd.2013.75.5.205
  39. Shimizu T, Shimizu S, Hattori R, Gabazza EC, Majima Y. In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells. Am J Respir Crit Care Med 2003;168:581-7. https://doi.org/10.1164/rccm.200212-1437OC