DOI QR코드

DOI QR Code

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

  • Jin, Fengri (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Li, Xin (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 : 2020.05.20
  • Accepted : 2020.07.13
  • Published : 2020.09.01

Abstract

In this study, diclofenac, a non-steroidal anti-inflammatory drug, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. The human respiratory epithelial NCI-H292 cells were pretreated with diclofenac for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of diclofenac on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Diclofenac suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest diclofenac regulates the gene expression and production of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

Keywords

Acknowledgement

This research was supported by NRF-2014R1A6A1029617 and NRF-2017R1C1B1005126, Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education.

References

  1. 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
  2. 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
  3. Dastidar, S. G., Ganguly, K., Chaudhuri, K. and Chakrabarty, A. N. (2000) The anti-bacterial action of diclofenac shown by inhibition of DNA synthesis. Int. J. Antimicrob. Agents 14, 249-251. https://doi.org/10.1016/S0924-8579(99)00159-4
  4. Fredriksson, L., Herpers, B., Benedetti, G., Matadin, Q., Puigvert, J. C., de Bont, H., Dragovic, S., Vermeulen, N. P, Commandeur, J. N., Danen, E., de Graauw, M. and van de Water, B. (2011) Diclofenac inhibits tumor necrosis $factor-{\alpha}$-induced nuclear $factor-{\kappa}B$ activation causing synergistic hepatocyte apoptosis. Hepatology 53, 2027-2041. https://doi.org/10.1002/hep.24314
  5. Fujisawa, T., Velichko, S., Thai, P., Hung, L. Y., Huang, F. and Wu, R. (2009) Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappa B paradigm. J. Immunol. 183, 6236-6243. https://doi.org/10.4049/jimmunol.0900614
  6. Garvin, L. M., Chen, Y., Damsker, J. M. and Rose, M. C. (2016) A novel dissociative steroid VBP15 reduces MUC5AC gene expression in airway epithelial cells but lacks the GRE mediated transcriptional properties of dexamethasone. Pulm. Pharmacol. Ther. 38, 17-26. https://doi.org/10.1016/j.pupt.2016.04.004
  7. 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. (2007) 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
  8. 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
  9. Ishinaga, H., Takeuchi, K., Kishioka, C., Suzuki, S., Basbaum, C. and Majima, Y. (2005) Pranlukast inhibits NF-kappaB activation and MUC2 gene expression in cultured human epithelial cells. Pharmacology 73, 89-96. https://doi.org/10.1159/000081294
  10. Karakawa, A., Fukawa, Y., Okazaki, M., Takahashi, K., Sano, T., Amano, H., Yamamoto, M. and Yamada, S. (2009) Diclofenac sodium inhibits NFkappaB transcription in osteoclasts. J. Dent. Res. 88, 1042-1047. https://doi.org/10.1177/0022034509346147
  11. 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
  12. Kim, J. O., Sikder, M. A., Lee, H. J., Rahman, M., Kim, J. H., Chang, G. T. and Lee, C. J. (2012) Phorbol ester or epidermal growth-factor-induced 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
  13. Kingsmore, K. M., Grammer, A. C. and Lipsky, P. E. (2020) Drug repurposing to improve treatment of rheumatic autoimmune inflammatory diseases. Nat. Rev. Rheumatol. 16, 32-52. https://doi.org/10.1038/s41584-019-0337-0
  14. Kurakula, K., Hamers, A. A., van Loenen, P. and de Vries, C. J. (2015) 6-Mercaptopurine reduces cytokine and Muc5ac expression involving inhibition of $NF{\kappa}B$ activation in airway epithelial cells. Respir. Res. 16, 73. https://doi.org/10.1186/s12931-015-0236-0
  15. Laos, S., Baeckstrom, D. and Hansson, G. C. (2006) Inhibition of NFkappaB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells. Int. J. Oncol. 28, 695-704.
  16. Lee, H. J., Lee, S. Y., Bae, H. S., Kim, J. H., Chang, G. T., Seok, J. H. and Lee, C. J. (2011) 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
  17. 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. (2015) 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
  18. Li, X., Jin, F., Lee, H. J. and Lee, C. J. (2020) Recent advances in the development of novel drug candidates for regulating the secretion of pulmonary mucus. Biomol. Ther. (Seoul) 28, 293-301. https://doi.org/10.4062/biomolther.2020.002
  19. 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
  20. Rogers, D. F. and Barnes, P. J. (2006) Treatment of airway mucus hypersecretion. Ann. Med. 38, 116-125. https://doi.org/10.1080/07853890600585795
  21. Rogers, D. F. (2007) Mucoactive agents for airway mucus hypersecretory diseases. Respir. Care 52, 1176-1193.
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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. (2014) 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
  27. Sprenger, L., Goldmann, T., Vollmer, E., Steffen, A., Wollenberg, B., Zabel, P. and Hauber, H. P. (2011) Dexamethasone and N-acetylcysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways. Pulm. Pharmacol. Ther. 24, 232-239. https://doi.org/10.1016/j.pupt.2010.11.003
  28. Takada, Y., Bhardwaj, A., Potdar, P. and Aggarwal, B. B. (2004) Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene 23, 9247-9258. https://doi.org/10.1038/sj.onc.1208169
  29. 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. 96, 3081-3086. https://doi.org/10.1073/pnas.96.6.3081
  30. Voynow, J. A. and Rubin, B. K. (2009) Mucins, mucus, and sputum. Chest 135, 505-512. https://doi.org/10.1378/chest.08-0412
  31. Wu, D. Y., Wu, R., Reddy, S. P., Lee, Y. C. and Chang, M. M. (2007) Distinctive epidermal growth factor receptor/extracellular regulated kinase-independent and -dependent signaling pathways in the induction of airway mucin 5B and mucin 5AC expression by phorbol 12-myristate 13-acetate. Am. J. Pathol. 170, 20-32. https://doi.org/10.2353/ajpath.2007.060452