Matrix Metalloproteinase in Idiopathic Pulmonary Fibrosis

특발성 폐섬유화증환자의 기관지폐포세척액 및 폐포대식세포 배양액의 Matrix metalloproteinase의 변화

  • Park, Joo-Hun (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Shim, Tae-Sun (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Lim, Chae-Man (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Koh, Youn-Suck (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Lee, Sang-Do (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Kim, Woo-Sung (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Kim, Won-Dong (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Kim, Dong-Soon (Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine)
  • 박주헌 (울산대학교 의과대학 서울중앙병원 내과학교실) ;
  • 심태선 (울산대학교 의과대학 서울중앙병원 내과학교실) ;
  • 임채만 (울산대학교 의과대학 서울중앙병원 내과학교실) ;
  • 이상도 (울산대학교 의과대학 서울중앙병원 내과학교실) ;
  • 고윤석 (울산대학교 의과대학 서울중앙병원 내과학교실) ;
  • 김우성 (울산대학교 의과대학 서울중앙병원 내과학교실) ;
  • 김원동 (울산대학교 의과대학 서울중앙병원 내과학교실) ;
  • 김동순 (울산대학교 의과대학 서울중앙병원 내과학교실)
  • Published : 2001.10.30

Abstract

Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

Acknowledgement

Supported by : 아산생명과학