[논문]필용방감길탕이 기도 뮤신의 분비, 생성, 유전자 발현 및 점액 과다 분비에 미치는 영향

김윤영; 민상연; 김장현

doi:10.7778/jpkm.2014.28.2.056

필용방감길탕이 기도 뮤신의 분비, 생성, 유전자 발현 및 점액 과다 분비에 미치는 영향
Effect of Piryongbanggamgil-tang on Airway Mucin Secretion, Production, Gene Expression and Hypersecretion of Mucus 원문보기

大韓韓方小兒科學會誌 = The journal of pediatrics of Korean medicine, v.28 no.2, 2014년, pp.56 - 71

김윤영 (하늘한방소아과한방재활의학과한의원) , 민상연 (동국대학교 한의과대학 소아과교실) , 김장현 (동국대학교 한의과대학 소아과교실)

Abstract ▼ AI-Helper

Objectives In this study, the author tried to investigate whether piryongbang-gamgil-tang (PGGT) significantly affect in vitro airway mucin secretion, PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production / gene expression from human airway epithelial cells and increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats. Materials and Methods For in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of PGGT to assess the effect of PGGT on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effect of PGGT on PMA- or EGFor 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 PGGT and treated with PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to assess both effect of PGGT on PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by ELISA and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). For in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered PGGT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assesed by using histopathological analysis after staining the epithelial tissue with alcian blue. Possible cytotoxicities of PGGT in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of PGGT were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering PGGT orally. Results (1) PGGT did not affect in vitro mucin secretion from cultured RTSE cells. (2) PGGT significantly inhibited PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. (3) PGGT decreased the amount of intraepithelial mucosubstances and showed the tendency of expectorating airway mucus already produced. (4) PGGT increased LDH release from RTSE cells. However, PGGT did not show in vivo liver and kidney toxicities and cytotoxicity to NCI-H292 cells. Conclusion The result from this study suggests that PGGT can regulate the production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of PGGT with their components should be further studied using animal experimental models that reflect the diverse pathophysiology of respiratory diseases through future investigations.

주제어

질의응답

핵심어	질문	논문에서 추출한 답변
	객담은 무엇인가?	객담은 有形의 痰, 狹義의 痰에 해당되고3), 타액, 혈청 단백질 삼출물, 박리된 상피세포들과 기도 점액의 혼합물로 구성되어 있는 병리적 물질로 기도 병리상태의 지표가 될 수 있다4). 정상적으로 분비되는 기도 점액은 섬모 운동과 호흡, 혈관 및 림프관에 의해 제거 또는 흡수되면서 인체에 유해한 물질을 제거하는 방어 작용을 하나5), 점액의 구성요소인 뮤신의 점탄성 변화로 객담 혹은 점액이 과다분비 되면 호흡기 생리 및 방어 작용에 영향을 주어 병리 현상을 유발할 수 있으며, 호흡기 질환의 예후를 악화시키는 주된 요인이 된다6-8).
	소아의 생리적 특징은?	소아는 생리적으로 臟腑嬌嫩하고 形氣未充한 특징을 보이며, 특히 肺常不足으로 衛外기능이 未固하여 六淫의 邪氣를 받기 쉬우므로 급성 호흡기 감염으로 인한 感冒, 咳嗽, 哮喘 등이 빈번하게 발생하고1), 肺의 宣降기능이 失調되어 氣機不利로 인한 津液의 輸布, 排泄에 장애가 유발되어 痰이 쉽게 형성된다2).

참고문헌 (54)

Kim DG, Kim YH, Kim JH, Park EJ, Baek JH, Lee SY, Lee JY, Chang GT. Donguisoagwahak. Jeongdam. 2002:28-30,244-6.
Jeongukhanuigwadaehak byeongrihakgyosil. Hanbangbyeongrihak. seoul:Iljongsa. 2002:69-81.
Jeongukhanuigwadaehak pegyenaegwahakgyosil. Donguipegyenaegwahak. seoul: Hanmunhwasa. 2002:102-14.
Lee CJ, Ko KH. Pathophysiologic characteristics of airway mucus-hypersecretory diseases and experimental models. J Appl Pharmacol. 1998;6 (1):1-8.
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.
Frigas E, Loegering DA, Solley GO, Farrow GM, Gleich GJ. Elevated levels of the eosinophil granule major basic protein in the sputum of patients with bronchial asthma. Mayo Clin Proc. 1981;56(6):345-53.

상세보기
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.

상세보기
Gleich GJ. The eosinophil and bronchial asthma: Current understanding. J Allergy Clin Immunol. 1990;85(2): 422-36.

상세보기
Rogers DF. Airway mucus hypersecretion in asthma: an undervalued pathology. Curr Opin Pharmacol. 2004;4(3):241-50.

상세보기
Mutschler E, Derendorf H. Drug actions. Boca Raton, Florida:CRC press. 1995:410-1.
Rogers DF, Barnes PJ. Treatment of airway mucus hypersecretion. Ann Med. 2006;38(2):116-25.

상세보기
Rogers DF. Mucociliary dysfunction in COPD: effect of current pharmacotherapeutic options. Pulm Pharmacol Ther. 2005;18(1):1-8.

상세보기
Huhjoon. Donguibogam. Donguibogamchulpansa. 2005: 202-9, 624-5.
Hwangdoyein. Bangyakhappyoen, Seoul:Namsandang. 2000:237-8.
Park HK, Chae BY. Experimental studies on the antiinflammatory, analgesic effect of Piryongbanggamgiltang and Gamipiryongbanggamgil-tang on rats and mice. KH Univ O Med J. 1981;4:285-94.
Min YT. Effect of gamgil-tang extract on the plasma cortisol concentration and plasma sodium concentration. J Korean Med Soc Herb Formul Study. 1990;1(1):173-82.
Kim DH. The effect of Gamgil-tang on lipopolysaccharide-induced NF- $\kappa{B}$ activation in raw 264.7 cell and acute lung injury in rats. College of Oriental Medicine, Dongeui University. Master's thesis. 2001.
Park MS, Son YJ, Lee YJ. The effect of Gamgil-tang and Gamigamgil-tang on antipyretics, anti-inflammation and discharge of phlegm. Korean J Herbology. 2002; 17(1):65-79.
Jin HJ, Kim NJ, Choi HJ, Jung HJ, Jung SK. Antiinflammatory effects, analgesic effects, antipyretic effects, anti-oxidative effects, and histamin permeation inhibition effects of modified Gamgil-tang per extraction method. Korean J Orient Int Med. 2008;29(3):554-66.
Kim KC. Possible requirement of collagen gel substratum for production of mucin-like glycoproteins by primary rabbit tracheal epithelial cells in culture. In Vitro. 1985;21(11):617-21.
Kim KC, Rearick JI, Nettesheim P, Jetten AM. Biochemical characterization of mucus glycoproteins synthesized and secreted by hamster tracheal epithelial cells in primary culture. J Biol Chem. 1985;260(7): 4021-7.
Kim KC, Brody JS. Gel contraction causes mucin release in primary hamster tracheal epithelial cells growing on a collagen gel. J Cell Biol. 1987;105:158a.
Wu R, Smith D. Continuous multiplication of rabbit tracheal epithelial cells in a defined, hormone-supplemented medium. In Vitro. 1982;18(9):800-12.

상세보기
Wu R, Nolan E, Turner C. Expression of tracheal differentiated function in serum-free hormone-supplemented medium. J Cell Physiol. 1985;125(2): 167-81.

상세보기
Ko KH, Lee CJ, Shin CY, Jo MJ, Kim KC. Inhibition of mucin release from airway goblet cells by polycationic peptides. Am J Physiol. 1999;277(4):L811-5.
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.
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.

상세보기
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.

상세보기
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.

상세보기
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.

상세보기
Harkema JR, Hotchkiss JA. In vivo effect of endotoxin on intraepithelial mucosubstances in rat pulmonary airways: quantitative histochemistry. Am J Pathol. 1992;141(2):307-17.
George JA, Cranz DL, Zicker S, Etchison JR, Dungworth DL, Plopper. An immunohistochemical characterization of rhesus monkey respiratoty secretions using monoclonal antibodies. Am Rev Resp Dis. 1985;132(3):556-63.
Kim YD, Kwon EJ, Park DW, Song SY, Yoon SK, Baek SH. Interleukin- $1\beta$ induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Mol Pharmacol. 2002;62(5):1112-8.

상세보기
Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR. New colorimetric cytotoxicity assay for anticancer drug screening. J Natl Cancer Inst. 1990;82(13): 1107-12.

상세보기
Gang YI, Jang JM. Silyongjonguisoagwahak. Sanghae: Sanghaegwahakgisulchulpansa. 1996:455-61.
Kang MS, Jang GT, Kim JH. A study on chronic or recurrent respiratory symptoms. J Pediatr Korean Med. 2002;16(2):83-99.
Ahn HS. Pediatrics. Seoul: Daehangyogwaseo. 2005: 606-40.
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.
Kim JM, Lee CJ, Park YC. Studies on the effects of selected oriental herbal medicines on inhibitory activity of airway mucus secretion. Korean J Orient Int Med. 2006;27(1):126-37.
Lee NY, Han JK, Kim YH. Effect of Gamitonggyu-tang on secretion of airway mucin and contractility of tracheal smooth mucsle. J Pediatr Korean Med. 2007;21(3): 109-24.
Kim HH. Hanuihakwonron. Seoul:Sungbosa. 2003: 352-8.
Yoon YG. Donguibangjecheobanghaeseol. Seoul: Uiseongdang. 2002:84.
Jeongukhanuigwadaehakbonchohakgyosu. Bonchohak. Seoul:younglimsa. 2000:127-8, 131-2, 142-3, 178-9, 192-3, 460-1, 540-1.
Lee SI, Ahn SI, Sin MH, Noh SH, Lee YJ, Kim SH. Hanyakimsangeungyong. Seoul:Jeontonguihakyoenguso. 1998:40-3, 52-3, 107-8, 114-6, 323-7, 472-3.
Kai H, Yoshitake K, Hisatsune A, Kido T, Isohama Y, Takahama K, Miyata T. Dexamethasone suppresses mucus production and MUC2 and MUC5AC gene expression by NCI-H292 cells. Am J Physiol. 1996; 271(3):L484-8.
Schmidt R, Hecker E. Autoxidation of phorbol esters under normal storage conditions. Cancer Res. 1975; 35(5):1375-7.

상세보기
Saitoh T, Dobkins KR. Protein kinase C in human brain and its inhibition by calmodulin. Brain Res. 1986; 379(1):196-9.

상세보기
Nam TH, Park YC. Effects of Seonbangpaedok-tang and Sigyeongcheongpye-tang on PMA-induced production of airway mucin and expression of MUC5AC. J Korean Orient Med. 2008;29(4):123-32.
Shim JJ. Signal transduction of MUC5AC expression in airway mucus hypersecretory desease. Tuberc Respir Dis. 2003;55(1):21-30.

원문보기 상세보기
Li D, Gallup M, Fan N, Szymkowski DE, Basbaum CB. Cloning of the amino-terminal and 5'-flanking region of the human MUC5AC mucin gene and transcriptional up-regulation by bacterial exoproducts. J Biol Chem. 1998;273(12):6812-20.

상세보기
Kim YH, Yoon HK, Kim CH, Ahn JH, Kwon SS, Kim YK, Kim KH, Moon HS, Park SH, Song JS, Cho KS. MUC5AC gene expression induced by cigarette smoke is mediated via a pathway involving ERK1/2 and p38 MAPK. Tuberc Respir Dis. 2005;58(6):590-9.

원문보기 상세보기
Kim SJ, Kang CM, You MB, Yoon HK, Kim YK, Kim KH, Moon HS, Park SH, Song JS. IP-10 decreases TNF- $\alpha$ induced MUC5AC expression in human airway epithelial cells: a possible relation with little sputum production in idiopathic pulmonary fibrosis. Tuberc Repir Dis. 2008;64:347-55.

원문보기 상세보기
Yu XY, Schofield BH, Croxton T, Takahashi N, Gabrielson EW, Spannhake EW. Physiologic modulation of bronchial epithelial cell barrier function by polycationic exposure. Am J Respir Cell Mol Biol. 1994;11(2):188-98.

상세보기
Freshny. Measurement of viability and cytotoxicity, In Culture of animal cells, 3rd ed. New York:Willey-Liss. 1994:288.

저자의 다른 논문 :

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증