Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF.

Abstract

The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis. The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MM P-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement. Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9. Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis.

• Authors: M T Henry, K McMahon, A J Mackarel, K Prikk, T Sorsa, P Maisi, R Sepper, M X Fitzgerald, C M O'Connor
• Journal: The European respiratory journal (Eur Respir J) Vol. 20 Issue 5 Pg. 1220-7 (Nov 2002) ISSN: 0903-1936 [Print] England
• PMID: 12449177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Collagenases
• Matrix Metalloproteinases
• Matrix Metalloproteinase 8
• Matrix Metalloproteinase 9

Topics

• Aged
• Blotting, Western
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Collagenases (metabolism)
• Female
• Humans
• Male
• Matrix Metalloproteinase 8 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Matrix Metalloproteinases (metabolism)
• Middle Aged
• Pulmonary Fibrosis (metabolism, pathology)
• Sarcoidosis, Pulmonary (metabolism, pathology)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)