Characterization of Matrix Metalloproteinase (MMP) expression and activity in the lungs of patients with Idiopathic Pulmonary Fibrosis (IPF)

Background: Matrix metalloproteinases (MMPs) are inducible zinc-dependent, secreted or cell surface endopeptidases that are centrally involved in extracellular matrix turnover. An imbalance of MMPs and their inhibitors (TIMPs) in the lung was recently suggested to contribute to the pathogenesis of interstitial lung diseases such as Idiopathic Pulmonary Fibrosis (IPF). Objective: In the present study we investigated the expression and activity of different MMPs and TIMP in the lungs of patients with IPF. Methods: Lung homogenates from IPF patients and healthy controls were analyzed for the expression and activity of gelatinases (MMP-2, MMP-9), collagenases (MMP-1, MMP-8) and TIMP-1 by western blotting and gelatin zymography. Furthermore, some preliminary in situ zymography (ISZ) studies were performed. Results: MMP-2 activity was strongly increased in IPF lungs as compared to healthy controls whereas no difference in MMP-9 activity could be observed. Reduced MMP-8 expression was observed in IPF lungs versus healthy controls, but no difference in MMP-1 expression could be observed. Interestingly, in all IPF samples analyzed, but only in 2 out of 5 healthy controls high TIMP-1 expression could be observed. ISZ revealed intense gelatinolytic and collagenolytic activity in lung sections from IPF patients. Conclusion: IPF lungs show a different MMP/TIMP expression and activity pattern as compared to healthy controls that might contribute to the alteration of the lung structure in IPF. Further studies (ISZ; laser-assisted microdissection of lung cells with subsequent characterization of MMP and TIMP specific RNA expression by real time PCR) are necessary to localize the sites of MMP/TIMP activity and to identify the cellular source of MMPs and TIMP in IPF lungs.