Tuberculosis and Respiratory Diseases

  • 제64권5호
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  • Pages.347-355
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  • 2008
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  • 1738-3536(pISSN)
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  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
권호 표지

IP-10에 의한 기도상피세포에서의 TNF-α 유도 MUC5AC발현 억제: 특발성폐섬유증 환자의 적은 객담과의 연관성

IP-10 Decreases TNF-α Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis

  • 김승준 (가톨릭대학교 의과대학 내과학교실) ;
  • 강춘미 (가톨릭대학교 의과대학 내과학교실) ;
  • 유문빈 (가톨릭대학교 의과대학 내과학교실) ;
  • 윤형규 (가톨릭대학교 의과대학 내과학교실) ;
  • 김영균 (가톨릭대학교 의과대학 내과학교실) ;
  • 김관형 (가톨릭대학교 의과대학 내과학교실) ;
  • 문화식 (가톨릭대학교 의과대학 내과학교실) ;
  • 박성학 (가톨릭대학교 의과대학 내과학교실) ;
  • 송정섭 (가톨릭대학교 의과대학 내과학교실)
  • Kim, Seung Joon (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kang, Chun Mi (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • You, Moon Bin (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Yoon, Hyung Kyu (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, Young Kyoon (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, Kwan Hyoung (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Moon, Hwa Sik (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Park, Sung Hak (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Song, Jeong Sup (Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
  • 투고 : 2008.03.24
  • 심사 : 2008.04.29
  • 발행 : 2008.05.30
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초록

연구배경: 특발성폐섬유증 환자의 전형적인 증상은 운동호흡곤란과 마른기침으로, 객담이 적은 원인에 대해서 아직까지 잘 알려져 있지 않다. Interferon-${\gamma}$ inducible protein-10 (IP-10)은 여러 호흡기질환과 관련되는데 폐 내로 염증을 유입시키는데 중요한 역할을 한다. 본 연구는 특발성폐섬유증 환자에서 객담이 적은 기전으로 IP-10이 연관성이 있는지에 대해 연구하였다. 방법: 특발성폐섬유증 환자를 대상으로 기관지폐포세척액에서 IP-10의 농도를 ELISA로 측정하였다. IP-10이 기도 점액소 발현에 미치는 영향을 간접적으로 알아보기 위해 NCI-H292 세포(점막표피모양 암종 세포주)에서 IP-10을 전처치한 이후 tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)로 자극하여 발현정도를 측정하였다. 이때 점액소 발현과 관련되는 기전으로 epidermal growth factor receptor-mitogen activated protein kinase (EGFR-MAPK)의 신호전달 경로를 알아 보았다. 결과: IP-10의 기관지폐포세척액내 농도는 특발성폐섬유증 환자가 건강 대조군에 비해 유의하게 높았다. IP-10의 전처치는 NCI-H292 세포에서 TNF-${\alpha}$ 유도 MUC5AC 점액소 발현을 감소시켰는데 이 때 EGFR-MAPK 신호전달 경로의 차단과 관련되었다. 결론: 특발성폐섬유증 환자의 적은 객담은 IP-10의 발현증가와 일부 관련 가능성이 있으며, 이때 IP-10의 작용은 MUC5AC 점액소 유전자 발현에 필요한 EGFR-MAPK 신호전달 경로의 차단과 관련될 것으로 생각한다.

Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

키워드

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