Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Effect of Platycodin D on Airway MUC5AC Mucin Production and Gene Expression Induced by Growth Factor and Proinflammatory Factor

  • Lee, Hyun-Jae (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Lee, Su-Yel (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Jeon, Byeong-Kyou (Department of Radiologic Technology, Daegu Health College) ;
  • Lee, Jae-Woo (LG Life Science) ;
  • Kim, Young-Sik (Department of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) ;
  • Lee, Mi-Nam (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Lee, Choong-Jae (Department of Pharmacology, School of Medicine, Chungnam National University)
  • Received : 2010.07.08
  • Accepted : 2010.07.19
  • Published : 2010.07.31
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Abstract

In this study, we tried to investigate whether platycodin D significantly affects MUC5AC mucin production and gene expression induced by epidermal growth factor (EGF), phorbol ester (PMA) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) from human airway epithelial cells. Confluent NCI-H292 cells were pretreated with varying concentrations of platycodin D for 30 min and then stimulated with EGF, PMA and TNF-$\alpha$ for 24h, respectively. MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA. The results were as follows: (1) Platycodin D was found to inhibit the production of MUC5AC mucin protein induced by EGF, PMA, and TNF-$\alpha$, respectively. (2) It also inhibited the expression of MUC5AC mucin gene induced by the same inducers. These results suggest that platycodin D can regulate mucin gene expression and production of mucin protein, by directly acting on human airway epithelial cells.

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References

  1. Ahn, K. S., Hahn, B. S., Kwack, K., Lee, E. B. and Kim, Y. S. (2006). Platycodin D-induced apoptosis through nuclear factor-kappaB activation in immortalized keratinocytes. Eur. J. Pharmacol. 537, 1-11. https://doi.org/10.1016/j.ejphar.2006.03.012
  2. Chung, J. W., Noh, E. J., Zhao, H. L., Sim, J. S., Ha, Y. W., Shin, E. M., Lee, E. B., Cheong, C. S. and Kim, Y. S. (2008). Anti-inflammatory activity of prosapogenin methyl ester of platycodin D via nuclear factor-kappaB pathway inhibition. Biol. Pharm. Bull. 31, 2114-2120. https://doi.org/10.1248/bpb.31.2114
  3. Chung, K. F. (2001). Cytokines in chronic obstructive pulmonary disease. Eur. Respir. J. Suppl. 34, 50-59.
  4. Cohn, L., Whittaker, L., Niu, N. and Homer, R. J. (2002). Cytokine regulation of mucus production in a model of allergic asthma. Novartis. Found. Symp. 248, 201-213. https://doi.org/10.1002/0470860790.ch13
  5. Ellis, E. F. (1985). Asthma in childhood. J. Allergy. Clin. Immunol. 72(Suppl), 526-539.
  6. Fischer, B. M., Rochelle, L. G., Voynow, J. A., Akley, N. J. and Adler, K. B. (1999). TNF-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. Am. J. Respir. Cell. Mol. Biol. 20, 413-422. https://doi.org/10.1165/ajrcmb.20.3.3393
  7. 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. (2007a). Carbenoxolone and triterpenoids inhibited mucin secretion from airway epithelial cells. Phytother. Res. 21, 462-465. https://doi.org/10.1002/ptr.2102
  8. 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. (2007b). 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
  9. 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
  10. Hewson, C. A., Edbrooke, M. R. and Johnston, S. L. (2004). 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. 344, 683-695. https://doi.org/10.1016/j.jmb.2004.09.059
  11. Jang, I. M. (2003). Treatise on asian herbal medicines. Haksulpyunsu-kwan in Research institute of natural products of Seoul National University, Seoul. pp. 2748.
  12. Kim, M. O., Moon, D. O., Choi, Y. H., Shin, D. Y., Kang, H. S., Choi, B. T., Lee, J. D., Li, W. and Kim, G. Y. (2008). Platycodin D induces apoptosis and decreases telomerase activity in human leukemia cells. Cancer Lett. 261, 98-107. https://doi.org/10.1016/j.canlet.2007.11.010
  13. Kim, Y. P., Lee, E. B., Kim, S. Y., Li, D., Ban, H. S., Lim, S. S., Shin, K. H. and Ohuchi, K. (2001). Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum. Planta Med. 67, 362-364. https://doi.org/10.1055/s-2001-14317
  14. 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
  15. 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
  16. 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
  17. Li, J. D., Dohrman, A. F., Gallup, M., Miyata, S., Gum, J. R., Kim, Y. S., Nadel, J. A., Prince, A. and Basbaum, C. B. (1997). Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc. Natl. Acad. Sci. U S A 94, 967-972. https://doi.org/10.1073/pnas.94.3.967
  18. Park, S. J., Kang, S. Y., Kim, N. S. and Kim, H. M. (2002). Phosphatidylinositol 3-kinase regulates PMA-induced differentiation and superoxide production in HL-60cells. Immunopharmacol. Immunotoxicol. 24, 211-226. https://doi.org/10.1081/IPH-120003751
  19. Rogers, D. F. and Barnes, P. J. (2006). Treatment of airway mucus hypersecretion. Ann. Med. 38, 116-125. https://doi.org/10.1080/07853890600585795
  20. Shao, M. X., Ueki, I. F. and Nadel, J. A. (2003). TNF-alpha converting enzyme mediated MUC5AC mucin expression in cultured human airway epithelial cells. Proc. Natl. Acad. Sci. U S A 100, 11618-11623. https://doi.org/10.1073/pnas.1534804100
  21. 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
  22. Song, K. S., Lee, W. J., Chung, K. C., Koo, J. S., Yang, E. J., Choi, J. Y. and Yoon, J. H. (2003). IL-1beta and TNF-alpha induced MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinase-MSK1-CREB activation in human airway epithelial cells. J. Biol. Chem. 278, 23243-23250. https://doi.org/10.1074/jbc.M300096200
  23. Takeyama, K., Dabbagh, K., Jeong, Shim, J., Dao-Pick, T., Ueki, I. F. and Nadel, J. A. (2000). Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor: role of neutrophils. J. Immunol. 164, 1546-1552. https://doi.org/10.4049/jimmunol.164.3.1546
  24. Takeyama, K., Dabbagh, K., Lee, H., Agusti, C., Lausier, J. A., Ueki, I. F., Grattan, K. M. and Nadel, J. A. (1999). Epidermal growth factor system regulates mucin production in airways. Proc. Natl. Acad. Sci. U S A 6, 3081-3086.
  25. Yu, J. S. and Kim, A. K. (2010). Platycodin D induces apoptosis in MCF-7 human breast cancer cells. J. Med. Food. 13, 298-305. https://doi.org/10.1089/jmf.2009.1226

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