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Triptolide Inhibits Lipopolysaccharide-Induced MUC5AC/5B Expression via Nuclear Factor-Kappa B in Human Airway Epithelial Cells

사람 호흡기 상피세포에서 Triptolide의 Nuclear Factor-Kappa B를 통한 Lipopolysaccharide로 유도된 MUC5AC/5B 발현 억제 효과

  • Seo, Bo Hyeon (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Choi, Tae Yeong (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Choi, Yoon Seok (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Bae, Chang Hoon (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Na, Hyung Gyun (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Song, Si-Youn (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Kim, Yong-Dae (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University)
  • 서보현 (영남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 최태영 (영남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 최윤석 (영남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 배창훈 (영남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 나형균 (영남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 송시연 (영남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 김용대 (영남대학교 의과대학 이비인후-두경부외과학교실)
  • Received : 2018.03.27
  • Accepted : 2018.06.28
  • Published : 2018.12.25

Abstract

Background and Objectives The representative mucin genes in the human airway are MUC5AC and MUC5B, which are regulated by several inflammatory and anti-inflammatory substances. Triptolide (TPL), udenafil, betulinic acid, changkil saponin, and glucosteroid are some of the many anti-inflammatory substances that exist. TPL is a diterpenoid compound from the thunder god vine, which is used in traditional Chinese medicine for treatment of immune inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. However, the effects of TPL on mucin expression of human airway epithelial cells have yet to be reported. Hence, this study investigated the effect of TPL on lipopolysaccharide (LPS)-induced MUC5AC and MUC5B expression in human airway epithelial cells. Subjects and Method The NCI-H292 cells and the primary cultures of human nasal epithelial cells were used to investigate the effects of TPL on LPS-induced MUC5AC and MUC5B expression using real-time polymerase chain reaction, enzyme immunoassay, and Western blot. Results TPL significantly decreased the LPS-induced MUC5AC and MUC5B mRNA expression and protein production. TPL also significantly decreased the nuclear factor-kappa B (NF-kB) phosphorylation. Conclusion These results suggest that TPL down regulates MUC5AC and MUC5B expression via inhibition of NF-kB activation in human airway epithelial cells. This study may provide important information about the biological role of triptolide on mucus-secretion in airway inflammatory diseases and the development of novel therapeutic agents for controlling such diseases.

Keywords

References

  1. Ali MS, Pearson JP. Upper airway mucin gene expression: a review. Laryngoscope 2007;117(5):932-8. https://doi.org/10.1097/MLG.0b013e3180383651
  2. Kim KC. Role of epithelial mucins during airway infection. Pulm Pharmacol Ther 2012;25(6):415-9. https://doi.org/10.1016/j.pupt.2011.12.003
  3. Park NK, Choi YS, Lee JH, Kim HS, Kim JK, Ahn JH, et al. Effect of udenafil on MUC5B expression in human airway epithelial cells. Korean J Otorhinolaryngol-Head Neck Surg 2013;56(8):501-5. https://doi.org/10.3342/kjorl-hns.2013.56.8.501
  4. Lee JG, Moon HJ, Kim SS, Kim CW, Yoon JH. Expression and regulation of MUC8 & MUC5AC by various cytokines in normal human nasal epithelial cells. Korean J Otolaryngol-Head Neck Surg 2001;44(6):600-5.
  5. Song EJ, Bae CH, Kim JY, Kim YW, Park SY, Song SY, et al. Effect of epigallocatechin-3-gallate on PMA-induced MUC5B expression in human airway epithelial cells. Clin Exp Otorhinolaryngol 2013;6(4):237-42. https://doi.org/10.3342/ceo.2013.6.4.237
  6. Lee JH, Kim GO, Na HG, Park NK, Kim HS, Kim JK, et al. Effect of anthocyanidin on MUC5AC and MUC5B expression in airway epithelial cells. Korean J Otorhinolaryngol-Head Neck Surg 2013;56(5):291-6. https://doi.org/10.3342/kjorl-hns.2013.56.5.291
  7. Borchers MT, Carty MP, Leikauf GD. Regulation of human airway mucins by acrolein and inflammatory mediators. Am J Physiol 1999;276(4 Pt 1):L549-55.
  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(5):1112-8. https://doi.org/10.1124/mol.62.5.1112
  9. Dabbagh K, Takeyama K, Lee HM, Ueki IF, Lausier JA, Nadel JA. IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. J Immunol 1999;162(10):6233-7.
  10. 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(3):683-95. https://doi.org/10.1016/j.jmb.2004.09.059
  11. Song SY, Seo YJ, Kim YW, Park SY, Bae CH, Kim YD. Effect of Onchocerca volvulus chitinase on MUC5B expression in human airway epithelial cells. Am J Rhinol Allergy 2013;27(1):3-7. https://doi.org/10.2500/ajra.2013.27.3830
  12. Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, et al. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther 2003;2(1):65-72.
  13. Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kB transcriptional activation. J Biol Chem 1999;274(19):13443-50. https://doi.org/10.1074/jbc.274.19.13443
  14. Zhao G, Vaszar LT, Qiu D, Shi L, Kao PN. Anti-inflammatory effects of triptolide in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 2000;279(5):L958-66. https://doi.org/10.1152/ajplung.2000.279.5.L958
  15. Wei D, Huang Z. Anti-inflammatory effects of triptolide in LPS-induced acute lung injury in mice. Inflammation 2014;37(4):1307-16. https://doi.org/10.1007/s10753-014-9858-5
  16. Kim HS, Choi YS, Lee JH, Park NK, Park CH, Lee YH, et al. Effect of betulinic acid on MUC5AC and MUC5B expression in airway epithelial cells. Korean J Otorhinolaryngol-Head Neck Surg 2014;57(8):526-32. https://doi.org/10.3342/kjorl-hns.2014.57.8.526
  17. Choi JH, Hwang YP, Han EH, Kim HG, Park BH, Lee HS, et al. Inhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorum root-derived saponin in A549 cells. Food Chem Toxicol 2011;49(9):2157-66. https://doi.org/10.1016/j.fct.2011.05.030
  18. Lee HJ, Lee SY, Bae HS, Kim JH, Chang GT, Seok JH, et al. Inhibition of airway MUC5AC mucin production and gene expression induced by epidermal growth factor or phorbol ester by glycyrrhizin and carbenoxolone. Phytomedicine 2011;18(8-9):743-7. https://doi.org/10.1016/j.phymed.2010.11.003
  19. Kim KD, Lee HJ, Lim SP, Sikder A, Lee SY, Lee CJ. Silibinin regulates gene expression, production and secretion of mucin from cultured airway epithelial cells. Phytother Res 2012;26(9):1301-7. https://doi.org/10.1002/ptr.3727
  20. 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(3):451-9. https://doi.org/10.2332/allergolint.11-OA-0411
  21. Qiu D, Kao PN. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the chinese medicinal herb tripterygium wilfordii Hook. f. Drugs R D 2003;4(1):1-18. https://doi.org/10.2165/00126839-200304010-00001
  22. Chen M, Lv Z, Zhang W, Huang L, Lin X, Shi J, et al. Triptolide suppresses airway goblet cell hyperplasia and Muc5ac expression via NF-kB in a murine model of asthma. Mol Immunol 2015;64(1):99-105. https://doi.org/10.1016/j.molimm.2014.11.001