Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Involvement of IKK/IkBα/NF-kB p65 Signaling into the Regulative Effect of Engeletin on MUC5AC Mucin Gene Expression in Human Airway Epithelial Cells

  • Hossain, Rajib (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Kim, Kyung-il (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 : 2022.06.30
  • Accepted : 2022.08.01
  • Published : 2022.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, we examined whether engeletin exerts an effect on the gene expression of MUC5AC mucin, in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with engeletin for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of engeletin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Engeletin suppressed the mRNA expression and production of MUC5AC mucin, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest engeletin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

Keywords

Acknowledgement

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

References

  1. Adler, K. B. and Li, Y. (2001) Airway epithelium and mucus: intracellular signaling pathways for gene expression and secretion. Am. J. Respir. Cell Mol. Biol. 25, 397-400. https://doi.org/10.1165/ajrcmb.25.4.f214
  2. 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-κB pathway. Phytother. Res. 33, 919-928. https://doi.org/10.1002/ptr.6284
  3. 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-kappaB paradigm. J. Immunol. 183, 6236-6243. https://doi.org/10.4049/jimmunol.0900614
  4. 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
  5. Huang, W. C., Wu, L. Y., Hu, S. and Wu, S. J. (2018) Spilanthol inhibits COX-2 and ICAM-1 expression via suppression of NF-kappaB and MAPK signaling in interleukin-1beta-stimulated human lung epithelial cells. Inflammation 41, 1934-1944. https://doi.org/10.1007/s10753-018-0837-0
  6. 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
  7. Jiang, X., Chen, L., Zhang, Z., Sun, Y., Wang, X. and Wei, J. (2018) Protective and therapeutic effects of engeletin on LPS-induced acute lung injury. Inflammation 41, 1259-1265. https://doi.org/10.1007/s10753-018-0773-z
  8. Jin, F., Li, X., Lee, H. J. and Lee, C. J. (2020) 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. Biomol. Ther. (Seoul) 28, 431-436. https://doi.org/10.4062/biomolther.2020.090
  9. 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
  10. 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-kB activation in airway epithelial cells. Respir. Res. 16, 73.
  11. Laos, S., Baeckstrom, D. and Hansson, G. C. (2006) Inhibition of NF-kappaB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells. Int. J. Oncol. 28, 695-704.
  12. Lee, J. W., Ryu, H. W., Lee, S. U., Kim, M. G., Kwon, O. K. and Kim, M. O. (2019) Pistacia weinmannifolia ameliorates cigarette smoke and lipopolysaccharide-induced pulmonary inflammation by inhibiting interleukin-8 production and NF-kappaB activation. Int. J. Mol. Med. 44, 949-959.
  13. 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
  14. 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
  15. Li, X., Jin, F., Lee, H. J. and Lee, C. J. (2021) Kaempferol regulates the expression of airway MUC5AC mucin gene via IκBα-NF-κB p65 and p38-p44/42-Sp1 signaling pathways. Biomol. Ther. (Seoul) 29, 303-310. https://doi.org/10.4062/biomolther.2020.149
  16. Lillehoj, E. R. and Kim, K. C. (2002) Airway mucus: its components and function. Arch. Pharm. Res. 25, 770-780. https://doi.org/10.1007/BF02976990
  17. Liu, Y., Zhang, B., Zhang, T., Wang, H., Peng, L. and Zhou, L. (2020) Effect of NF-kappaB signal pathway on mucus secretion induced by atmospheric PM 2.5 in asthmatic rats. Ecotoxicol. Environ. Saf. 190, 110094.
  18. Nie, Y. C., Wu, H., Li, P. B., Xie, L. M., Luo, Y. L. and Shen, J. G. (2012) Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IkappaB-NF-kappaB signaling pathways. Eur. J. Pharmacol. 690, 207-213. https://doi.org/10.1016/j.ejphar.2012.06.040
  19. Rose, M. C. and Voynow, J. A. (2006) Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol. Rev. 86, 245-278. https://doi.org/10.1152/physrev.00010.2005
  20. Seo, H. S., Sikder, M. A., Lee, H. J., Ryu, J. and Lee, C. J. (2014) Apigenin inhibits tumor necrosis factor-α-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
  21. Serafini, M., Peluso, I. and Raguzzini, A. (2010) Flavonoids as anti-inflammatory agents. Proc. Nutr. Soc. 69, 273-278. https://doi.org/10.1017/S002966511000162X
  22. Shang, J., Liu, W., Yin, C., Chu, H. and Zhang, M. (2019) Cucurbitacin E ameliorates lipopolysaccharide-evoked injury, inflammation and MUC5AC expression in bronchial epithelial cells by restraining the HMGB1-TLR4-NF-kappaB signaling. Mol. Immunol. 114, 571-577. https://doi.org/10.1016/j.molimm.2019.09.008
  23. 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
  24. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S. and Boyd, M. R. (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82, 1107-1112. https://doi.org/10.1093/jnci/82.13.1107
  25. 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
  26. Tian, Q., Wang, G., Zhang, Y., Zhang, F., Yang, L. and Liu, Z. (2019) Engeletin inhibits Lipopolysaccharide/d-galactosamine-induced liver injury in mice through activating PPAR-gamma. J. Pharmacol. Sci. 140, 218-222. https://doi.org/10.1016/j.jphs.2019.06.011
  27. Wu, H., Zhao, G., Jiang, K., Li, C., Qiu, C. and Deng, G. (2016) Engeletin alleviates lipopolysaccharide-induced endometritis in mice by inhibiting TLR4-mediated NF-kappaB activation. J. Agric. Food Chem. 64, 6171-6178. https://doi.org/10.1021/acs.jafc.6b02304
  28. 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
  29. Xu, J., Li, X., Zhang, P., Li, Z. L. and Wang, Y. (2005) Anti-inflammatory constituents from the roots of Smilax bockiiwarb. Arch. Pharm. Res. 28, 395-399. https://doi.org/10.1007/BF02977667