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Effect of Haepyoijin-tang on Airway Mucin Secretion, Production, Gene Expression and Hypersecretion of Mucus

해표이진탕이 기도 뮤신의 분비, 생성 및 유전자 발현에 미치는 영향

  • Suk, Yun Hee (Department of Pediatrics, College of Oriental Medicine, Dongguk University) ;
  • Min, Sang Yeon (Department of Pediatrics, College of Oriental Medicine, Dongguk University) ;
  • Kim, Jang Hyun (Department of Pediatrics, College of Oriental Medicine, Dongguk University)
  • 석연희 (동국대학교 한의과대학 소아과교실) ;
  • 민상연 (동국대학교 한의과대학 소아과교실) ;
  • 김장현 (동국대학교 한의과대학 소아과교실)
  • Received : 2015.07.31
  • Accepted : 2015.08.17
  • Published : 2015.08.31

Abstract

Objectives : In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Methods : Hypersecretion of airway mucus was induced by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered HIJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was evaluated using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of HIJ was evaluated by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering HIJ orally. At the same time, the effect of HIJ on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of HIJ and treated with ATP ($200{\mu}M$), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results : (1) HIJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) HIJ did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. (3) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin gene expression from NCI-H292 cells. Conclusions : The result from the present study suggests that HIJ might control the production and gene expression of airway mucin observed in various respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of HIJ with their diverse components should be further investigated using animal experimental models that can reflect the pathophysiology of airway diseases through future studies.

Keywords

References

  1. Kim KB, Kim DG, Kim YH, Kim JH, Min SY, Park EJ, Baek JH, Yu SA, Lee SY, Lee JY, Lee HJ, Chang GT, Chai JW, Han YJ, Han JK. Hanbangsoacheongsonyeonuihak. Seoul: Ui Sung Dang. 2010:37-40, 346-69, 744.
  2. Hong CE. Textbook of pediatrics, 9th ed. Seoul: Korea Textbook Publishing Co. 2007:588-90, 594-5, 613.
  3. The korean academy of pediatric allergy and respiratory disease. Pediatric allergy immunology pulmonology. Seoul: koonjachulpansa. 2005:267-8, 350, 354.
  4. Lee CJ. Effects of poly - L - arginine on the mucin release from airway goblet cells of hamster and on the mucosubstances of airway goblet cells of rat. Appl Pharmacol. 2001;9(4):263.
  5. Newhouse MT, Biennenstock J. Respiratory tract defense mechanism. In: Baum GL, Wolinsky E ed. Textbook of pulmonary disease. 4th ed. Boston: Little, Brown and Company. 1994:2-47.
  6. Lee CJ. Specificity in the inhibition of mucin release from airway goblet cells by polycationic peptides. Appl Pharmacol. 2001;9(3):218-23.
  7. Mutschler E, Derendorf H. Drug actions. Boca Raton, Florida: CRC press. 1995:410-1.
  8. Rogers DF. Airway mucus hypersecretion in asthma: anundervalued pathology? Curr Opin Pharmacol. 2004;4(3):241-50. https://doi.org/10.1016/j.coph.2004.01.011
  9. Culpitt SV, Rogers DF, Traves SL, Barnes PJ, Donnelly LE. Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma. Respir Med. 2005;99(6):703-10. https://doi.org/10.1016/j.rmed.2004.10.022
  10. The korean academy of tuberculosis and respiratory disease. pneumology. Seoul: koonjachulpansa. 2004:16, 83, 297.
  11. Mae DD. Junggukuihaksaryak. Sanseo: Sanseoinminchulpansa. 1979:243.
  12. Sin JY. Bangyakhappyeonhaeseol. Seoul: Jeontonguihakyeonguso. 1988:133.
  13. Park DI, Lee GT. The effects of Haepyoyijintang on the pulmonary injury caused by SO2 in rats. J Korean Orient Med. 1996;17(2):178-90.
  14. Park CS, Han SH. Effects of Haepyoyangjintang and Haepyoejintang extract on the contraction of isolated guinea pig trachea smooth muscle. J Korean Orient Int Med. 1990;11(2):68-79.
  15. Baek DJ, Jung HJ, Rhee HK, Jung SK, The effects of Haepyoijin-tang on the cytokines in asthma model. J Korean Orient Med. 2000;21(3):57-67.
  16. Kim MS, Pack DI. The effects of Kamihaepyoijin-tang on the respiratory patterns and tracheal tissues in allergic asthma. Korean J Orient Physiol Pathol. 2002;16(3):557-62.
  17. Heo J. Dongeuibogam. Seoul: Namsandang. 1998:100-4, 108-9, 732.
  18. Pon DJ, van Staden CJ, Boulet L, Roger IW. Hyperplastic effects of aerosolized sodium metasulfite on rat airway mucus-secretory epithelial cells. Can J Physiol Pharmacol. 1994;72(9):1025-30. https://doi.org/10.1139/y94-143
  19. Lee CJ. Effects of poly-L-arginine on the mucin release from airway goblet cells of hamster and on the mucosubstances of airway goblet cells of rat. J Appl Pharmacol. 2001;9(4):263-9.
  20. St. George JA, Cranz DL, Zicker S, Etchison JR, Dungworth DL and Plopper. An immunohistochemical characterization of Rhesus monkey respiratoty secretions using monoclonal antibodies. Am Rev Resp Dis. 1985;132(3):556-63.
  21. Harkema JR, Hotchkiss JA. In vivo effect of endotoxin on intraepithelial mucosubstances in rat pulmonary airways: quantitative histochemistry. Am J Pathol. 1992;141(2):307-31.
  22. Shao MXG, Ueki IF, Nadel JA. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci USA. 2003;100(20):11618-23.
  23. Song KS, Lee WJ, Chung KC, Koo JS, Yang EJ, Choi JY, Yoon JH. Interleukin-$1{\beta}$ and tumor necrosis factor-alpha Induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells. J Biol Chem. 2003;278(26):23243-50. https://doi.org/10.1074/jbc.M300096200
  24. Karlinsey J, Stamatoyannopoulos G, Enver T. Simultaneous purification of DNA and RNA from small numbers of eukaryotic cells. Anal Biochem. 1989;180(2):303-6. https://doi.org/10.1016/0003-2697(89)90435-1
  25. Gong YI, Jang GM. Silyongjungeuiagwahak. Shanghai:Sanghaegwahakgisulchulpansa. 1996:455-61.
  26. Kang MS, Jang GT, Kim JH. A study on chronic or recurrent respiratory symptoms. J Pediatr Korean Med. 2002;16(2):83-99.
  27. Han JK, Kim YH. Health care utilization of pediatrics outpatients in the oriental hospital. J Pediatr Korean Med. 2001;15(2):209-20.
  28. Choi MH, Kim DG, Lee JY. A study of the chief complaint of pediatric outpatients in the Kyung Hee oriental medicine hospital . J Pediatr Korean Med. 2010;24(3):121-37.
  29. Lee CJ, Ko KH. Pathophysiologic characteristics of airway mucus-hypersecretory diseases and experimental models. J Appl Pharmacol. 1998;6(1):1-8.
  30. Lee JC. Formation of airway mucus; synthesis, exocytosis and dilution of Gel-forming mucins. Korean Acad Asthma Allergy Clin Immunol. 2012:32(2):73-80.
  31. Voynow JA, Rubin BK. Mucins, mucus, and sputum. Chest. 2009;135(2):505-12. https://doi.org/10.1378/chest.08-0412
  32. Jung CH, Han JK, Kim YH. Effects of Bojungikgitang-gamibang and Seonbangpaedok-tang on secretion of airway mucus and expression of mucin gene. J Pediatr Korean Med. 2007;21(3):33-55.
  33. Hanbangbyeongrihak gyojaepyeonchanwiwonhoe. Hanbangbyeongrihak. Seoul: Hanuimunhwasa. 2007:94-102.
  34. Jeongukhanuikwadaehak gyenaekwagyosil. Donguipyegyenaekwahak. Seoul: Hanmunhwasa. 2002:102-14.
  35. Jeongukhanuikwadaehak bonchohakgyosil. bonchohak. Seoul: Yeonglimsa. 2000:154-6, 158-9, 225-6, 348-50, 487, 499-500, 515-6, 518, 521-2, 586-8.
  36. Lee SI, An DG, Sin MG, No SH, Lee YD, Kim SH. Hanyakimsangeungyong. Seoul: Jeontonguihakyeonguso. 1998:36-7, 39-40, 151-3, 323-5, 393, 463-4, 472, 475-647, 748.
  37. Lee SY. The inhibitory effects of epidermal growth factor receptor inhibitor (erlotinib) in a mouse model of smoking. Korean J Orient Int Med. 2009;77(4):940.
  38. Shim JJ. Signal transduction of MUC5AC expression in airway mucus hypersecretory desease. Tuberc Respir Dis. 2003;55(1):26.
  39. Song KS, Lee WJ, Chung KC, Koo JS, Yang EJ, Choi JY, Yoon JH. Interleukin-1beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells. J Biol Chem. 2003;278(26):23243-50. https://doi.org/10.1074/jbc.M300096200

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