The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
권호 표지

Protective Effects of Gamipalmi-hwan on Elastase-induced Apoptosis of A549 Cells

가미팔미환(加味八味丸)의 elastase 유도성 A549 세포사멸에 대한 보호효과

  • Oh, Ji-Seok (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University) ;
  • Park, Yang-Chun (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University)
  • 오지석 (대전대학교 한의과대학 폐계내과학교실) ;
  • 박양춘 (대전대학교 한의과대학 폐계내과학교실)
  • Received : 2010.01.15
  • Accepted : 2010.03.02
  • Published : 2010.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: This study aimed to evaluate the protective effects of Gamipalmi-hwan (GPH) on elastase-induced lung cell injury. Materials and Methods: As an in vitro model of emphysema, the current study was performed to investigate potential activity of GPH in regulating injury responses of A549 human type II cell line mediated by elastase treatment. Results: GPH treatment increased the number of A549 cells which was reduced by elastase digestion. Elastin protein level, which was reduced by elastase treatment, was increased by GPH treatment. Labeling intensity with caspase 3 protein in elastase-treated cells was reduced by GPH treatment. Both Erk1/2 and Cdc2 protein levels, which were decreased by elastase treatment, were increased to a level similar to that of the normal cells. mRNA levels encoding IL-$1{\beta}$ and TNF-$\alpha$ were increased by elastase and then down-regulated by GPH. Conclusion: The present data suggest that A549 cells are subjected to inflammatory damage by elastase and can be recovered by GPH treatment. Further studies examining the protective activity of GPH in elastase-treated lung tissue would be useful for therapeutic strategies of emphysema treatment.

Keywords

References

  1. Korea National Statistical Office, Republic of Korea [Internet]. Dajeon: Korea National Statistical Office; c1996-[cited 2008 Mar]. Available from: http://www.nso.go.kr
  2. Kim DS, Kim YS, Jung KS, Chang JH, Lim CM, Lee JH, et al. Korean Academy of Tuberculosis and Respiratory Diseases. Prevalence of chronic obstructive pulmonary disease in Korea: a population-based spirometry survey. Am J Respir Crit Care Med. 2005 Oct 1;172(7):842-7. https://doi.org/10.1164/rccm.200502-259OC
  3. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532-55. https://doi.org/10.1164/rccm.200703-456SO
  4. Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nat Med 1998;4(11):1241-3. https://doi.org/10.1038/3218
  5. Chang J. Pharmacologic treatment of COPD. Tuberculosis and Respiratory Diseases. 2005;59(3):231-42.
  6. 전국한의과대학 폐계내과학교실. 동의폐계내과학. 서울: 한문화사. 2002:338-46.
  7. 허준. 동의보감. 서울: 남산당. 1986:147.
  8. 전국한의과대학 본초학교실. 本草學. 서울: 영림사. 1994:370-568.
  9. Lim DH, L JE, Han YJ, Hwang JH, Cho CJ, Bae HH, et al. Effects of HaengSoTang (HST), Gami-PalMiHwan (GPMH) on mucin secretion from airway goblet cells. Korean J Orient Int. 2005;26(1):221-8.
  10. Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease NHLBI/WHO Workshop report. Rev. ed. 2003.
  11. Kim HK, Lee SD. Pathophysiology of Chronic Obstructive Pulmonary Disease. Tuberculosis and Respiratory Diseases. 2005;59(1):5-13.
  12. Lucey EC, Goldstein RH, Stone PJ, Snider GL. Remodeling of alveolar walls after elastase treatment of hamsters. Results of elastin and collagen mRNA in situ hybridization. Am J Respir Crit Care Med. 1998;158(2):555-64. https://doi.org/10.1164/ajrccm.158.2.9705021
  13. Snider GL, Lucey EC, Stone PJ. Pitfalls in antiprotease therapy of emphysema. Am J Respir Crit Care Med. 1994;150(6 Pt 2):S131-7.
  14. Ranes J, Stoller JK. A review of alpha-1 antitrypsin deficiency. Semin Respir Crit Care Med. 2005;26(2):154-66. https://doi.org/10.1055/s-2005-869536
  15. Suki B, Bates JH. Extracellular matrix mechanics in lung parenchymal diseases. Respir Physiol Neurobiol. 2008;163(1-3):33-43. https://doi.org/10.1016/j.resp.2008.03.015
  16. Gardi C, Arezzini B, Martorana PA. Testing of compounds in models of pulmonary emphysema. Curr Med Chem. 2008;15(8):803-8. https://doi.org/10.2174/092986708783955536
  17. Churg A, Wright JL. Animal models of cigarette smoke-induced chronic obstructive lung disease. Contrib Microbiol. 2007;14:113-25.
  18. Grutter MG. Caspases: key players in programmed cell death. Curr Opin Struct Biol. 2000;10(6):649-55. https://doi.org/10.1016/S0959-440X(00)00146-9
  19. Rossi AG, Sawatzky DA, Walker A, Ward C, Sheldrake TA, Riley NA, et al. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med. 2006;12(9):1056-64. https://doi.org/10.1038/nm1468
  20. Budd RC. Activation-induced cell death. Curr Opin Immunol. 2001;13(3):356-62. https://doi.org/10.1016/S0952-7915(00)00227-2
  21. Robertson JD, Orrenius S. Molecular mechanisms of apoptosis induced by cytotoxic chemicals. Crit Rev Toxicol. 2000;30(5):609-27. https://doi.org/10.1080/10408440008951122
  22. Halestrap AP, Doran E, Gillespie JP, O'Toole A. Mitochondria and cell death. Biochem Soc Trans. 2000;28(2):170-7.
  23. Segal RA, Greenberg ME. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci. 1996;19:463-89. https://doi.org/10.1146/annurev.ne.19.030196.002335
  24. Meloche S, Pouyssegur J. The ERK1/2 mitogenactivated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene. 2007;26(22):3227-39. https://doi.org/10.1038/sj.onc.1210414
  25. Bogoyevitch MA, Court NW. Counting on mitogen-activated protein kinases--ERKs 3, 4, 5, 6, 7 and 8. Cell Signal. 2004;16(12):1345-54. https://doi.org/10.1016/j.cellsig.2004.05.004
  26. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153-83. https://doi.org/10.1210/er.22.2.153
  27. Tu H, Rondard P, Xu C, Bertaso F, Cao F, Zhang X, et al. Dominant role of GABAB2 and Gbetagamma for GABAB receptor-mediated-ERK1/2/CREB pathway in cerebellar neurons. Cell Signal. 2007;19(9):1996-2002. https://doi.org/10.1016/j.cellsig.2007.05.004
  28. Canon E, Cosgaya JM, Scsucova S, Aranda A. Rapid effects of retinoic acid on CREB and ERK phosphorylation in neuronal cells. Mol Biol Cell. 2004;15(12):5583-92. https://doi.org/10.1091/mbc.E04-05-0439
  29. Doree M, Hunt T. From Cdc2 to Cdk1: when did the cell cycle kinase join its cyclin partner? J Cell Sci. 2002;115(Pt 12):2461-4.
  30. Nebreda AR. CDK activation by non-cyclin proteins. Curr Opin Cell Biol. 2006;18(2):192-8. https://doi.org/10.1016/j.ceb.2006.01.001
  31. Goga A, Yang D, Tward AD, Morgan DO, Bishop JM. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med. 2007;13(7):820-7. https://doi.org/10.1038/nm1606
  32. Sapey E, Ahmad A, Bayley D, Newbold P, Snell N, Rugman P, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD. J Clin Immunol. 2009;29(4):508-16. https://doi.org/10.1007/s10875-009-9286-8