해표이진탕이 기도 뮤신의 분비, 생성 및 유전자 발현에 미치는 영향
Effect of Haepyoijin-tang on Airway Mucin Secretion, Production, Gene Expression and Hypersecretion of Mucus
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Objectives In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-α-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 SO2 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-α-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 μM), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-α (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-α-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-α-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-α-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.
Abstract
Objectives In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-α-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 SO2 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-α-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 μM), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-α (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-α-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-α-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-α-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.
참고문헌 (39)
- Kim KB, "Hanbangsoacheongsonyeonuihak", pp.37~40 (2010), Ui Sung Dang
- Hong CE, "Textbook of pediatrics", pp.588~590 (2007), Korea Textbook Publishing Co
- The korean academy of pediatric allergy and respiratory disease, "Pediatric allergy immunology pulmonology", pp.267~268 (2005), koonjachulpansa
- 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, 9(4), pp.263~ (2001)
- Newhouse MT, "Textbook of pulmonary disease", pp.2~47 (1994), Little, Brown and Company
- Lee CJ, "Specificity in the inhibition of mucin release from airway goblet cells by polycationic peptides", Appl Pharmacol, 9(3), pp.218~223 (2001)
- Mutschler E, "Drug actions", pp.410~411 (1995), CRC press
- Rogers DF, "Airway mucus hypersecretion in asthma: anundervalued pathology?", Curr Opin Pharmacol, 4(3), pp.241~250 (2004)
- Culpitt SV, "Sputum matrix metalloproteases : comparison between chronic obstructive pulmonary disease and asthma", Respir Med, 99(6), pp.703~710 (2005)
- The korean academy of tuberculosis and respiratory disease, "pneumology", pp.16~ (2004), koonjachulpansa
- Mae DD, "Junggukuihaksaryak", pp.243~ (1979), Sanseoinminchulpansa
- Sin JY, "Bangyakhappyeonhaeseol", pp.133~ (1988), Jeontonguihakyeonguso
- Park DI, "The effects of Haepyoyijintang on the pulmonary injury caused by SO2 in rats", J Korean Orient Med, 17(2), pp.178~190 (1996)
- Park CS, "Effects of Haepyoyangjintang and Haepyoejintang extract on the contraction of isolated guinea pig trachea smooth muscle", J Korean Orient Int Med, 11(2), pp.68~79 (1990)
- Baek DJ, "The effects of Haepyoijin-tang on the cytokines in asthma model", J Korean Orient Med, 21(3), pp.57~67 (2000)
- 김민수, "加味解表二陳湯이 알레르기 喘息 白鼠의 呼吸 樣相과 氣管 組織에 미치는 影響", 동의생리병리학회지, 16(3), pp.24~562 (2002), 한의병리학회
- Heo J, "Dongeuibogam", pp.100~104 (1998), Namsandang
- Pon DJ, "Hyperplastic effects of aerosolized sodium metasulfite on rat airway mucus-secretory epithelial cells", Can J Physiol Pharmacol, 72(9), pp.1025~1030 (1994)
- 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, 9(4), pp.263~269 (2001)
- St. George JA, "An immunohistochemical characterization of Rhesus monkey respiratoty secretions using monoclonal antibodies", Am Rev Resp Dis, 132(3), pp.556~563 (1985)
- Harkema JR, "In vivo effect of endotoxin on intraepithelial mucosubstances in rat pulmonary airways : quantitative histochemistry", Am J Pathol, 141(2), pp.307~331 (1992)
- Shao MXG, "Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells", Proc Natl Acad Sci USA, 100(20), pp.11618~11623 (2003)
- Song KS, "Interleukin-1β and tumor necrosis factor-alpha Induce MUC5AC overexpression through a mecha nism involving ERK", p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells, 2003, pp.278(26), 23243~23250
- Karlinsey J, "Simultaneous purification of DNA and RNA from small numbers of eukaryotic cells", Anal Biochem, 180(2), pp.303~306 (1989)
- Gong YI, "Silyongjungeuiagwahak", pp.455~461 (1996), Sanghaegwahakgisulchulpansa
- Kang MS, "A study on chronic or recurrent respiratory symptoms", J Pediatr Korean Med, 16(2), pp.83~99 (2002)
- Han JK, "Health care utilization of pediatrics outpatients in the oriental hospital", J Pediatr Korean Med, 15(2), pp.209~220 (2001)
- 최민형, "경희의료원 한방소아·청소년과 외래 환자의 주소증에 대한 연구 (2009년 3월~2010년 2월)", 대한한방소아과학회지, 24(3), pp.121~137 (2010), 대한한방소아과학회
- Lee CJ, "Pathophysiologic characteristics of airway mucus-hypersecretory diseases and experimental models", J Appl Pharmacol, 6(1), pp.1~8 (1998)
- 이재천, "기도 점액의 생성; 점액소의 합성, 분비 및 희석", 천식 및 알레르기, 32(2), pp.73~80 (2012), 대한천식알레르기학회[DOI]
- Voynow JA, "Mucins, mucus, and sputum", Chest, 135(2), pp.505~512 (2009)
- 정창호, "補中益氣湯 加味方과 仙方敗毒湯이 기도 점액의 분비와 뮤신 유전자발현에 미치는 영향", 대한한방소아과학회지, 21(3), pp.33~55 (2007), 대한한방소아과학회
- Hanbangbyeongrihak gyojaepyeonchanwiwonhoe, "Hanbangbyeongrihak", pp.94~102 (2007), Hanuimunhwasa
- Jeongukhanuikwadaehak gyenaekwagyosil, "Donguipyegyenaekwahak", pp.102~114 (2002), Hanmunhwasa
- Jeongukhanuikwadaehak bonchohakgyosil, "bonchohak", pp.154~156 (2000), Yeonglimsa
- Lee SI, "Hanyakimsangeungyong", pp.36~37 (1998), Jeontonguihakyeonguso
- Lee SY, "The inhibitory effects of epidermal growth factor receptor inhibitor (erlotinib) in a mouse model of smoking", Korean J Orient Int Med, 77(4), pp.940~ (2009)
- 심재정, "기도의 점액 과분비 질환에서 MUC5AC의 발현의 신호 전달 경로에 관한 연구", Tuberculosis and Respiratory Diseases, 55(1), pp.21~30 (2003), 대한결핵및호흡기학회
- Song KS, "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, 2003, pp.278(26), 23243~23250