Matrix Metalloproteinase in Idiopathic Pulmonary Fibrosis

Park, Joohun; Shim, Tae Sun; Lim, Chae Man; Koh, Younsuck; Lee, Sang Do; Kim, Woo Sung; Kim, Won Dong; Kim, Dong Soon

Abstract

BACKGROUND
Matrix metalloproteinase(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±1.73 years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age: 63.6±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 ans 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±0.28) followed by the stable group (0.46±0.13) and the controls (0.08±0.09). which was statistically significant. The MMP-9 level of the IPF (0.31±0.058) and the stable group (0.22±0.078) were higher than that of the control group (0.002±0.004). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group (0.80±0.10) than in the control group (0.23±0.081) The MMP-1 level was also higher in both the IPF (36.34±8.62 µg/ml) and stable group (20.83±8.53 µg/ml) compared to the control group (2.80±1.05 µg/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.