Metalloproteinases MMP-9, MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 in peripheral transbronchial lung biopsies of patients with sarcoidosis

INTRODUCTION The imbalance between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a granulomatous inflammatory disease which may lead to lung fibrosis. OBJECTIVES The aim of the study was to verify whether the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in peripheral lung biopsies of patients with sarcoidosis correlate with lung function tests, radiological pattern, and bronchoalveolar lavage (BAL) cells. We compared the expression of MMPs and TIMPs between patients with sarcoid-positive vs. -negative biopsy and fibrosing vs. non-fibrosing high-resolution computed tomography (HRCT) pattern. PATIENTS AND METHODS We examined patients with histologically proven stage II and III sarcoidosis (n = 17). Immunohistochemistry with antibodies against the studied molecules was performed in the lung and bronchial tissue specimens obtained from transbronchial lung biopsies. The radiological pattern was evaluated based on HRCT. The total cell number and percentage of cells were calculated in the BAL samples. RESULTS MMPs and TIMPs were present in the cells of sarcoid granuloma, and were more prevalent in the parenchyma than in the bronchi We found no correlation between MMP-9, MMP-2, TIMP-1, TIMP-2 and HRCT pattern or BAL cells. There were inverse associations between MMP-9 and FEV1 (% predicted), and also between MMP-2 and maximal expiratory flow 25-75% (L and % predicted) in patients with sarcoidosis diagnosed by transbronchial lung biopsy. There were no differences in the measured parameters between patients with and without fibrotic changes and between those with negative vs. positive lung biopsy results. CONCLUSION Our study provides an indirect evidence for a potential involvement of MMPs/TIMPs in the sarcoid inflammation of the distal airways.