QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.105544v1 318/2/741    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Birrell, M. A. Articles by Belvisi, M. G. Search for Related Content PubMed PubMed Citation Articles by Birrell, M. A. Articles by Belvisi, M. G.

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Role of Matrix Metalloproteinases in the Inflammatory Response in Human Airway Cell-Based Assays and in Rodent Models of Airway Disease

Respiratory Pharmacology Section, Airway Disease Department, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom (M.A.B., S.W., A.D., J.D.A., M.G.B.); and Royal Brompton & Harefield Hospital, London, United Kingdom (S.H.-Y.)

Since the discovery of the first matrix metalloproteinase (MMP), this ever-growing family of proteinases has been the subject of intense research. Although it was initially believed that MMPs were solely involved in matrix turnover and degradation, there are now data suggesting MMPs are actively involved in the inflammatory process. In previous studies, we have demonstrated an increase in MMP expression in human cell-based assays and in preclinical rat models of airway inflammation. Therefore, the aim of this study was to characterize the role of MMPs in these models by profiling the impact of a broad-spectrum MMP inhibitor. In lipopolysaccharide (LPS)-stimulated THP-1 cells and primary human lung tissue macrophages, the MMP inhibitor had no significant effect on the release of tumor necrosis factor-, interleukin (IL)-8, IL-1, growth-regulated oncogene-, macrophage inflammatory protein-1, or IL-6 whereas dexamethasone has a significant impact on all cytokines from both cell types. Similarly, in the more biologically complex LPS-driven rat model of airway inflammation, the MMP inhibitor did not have an impact on mediator release and cellular burden. The compound did, however, significantly reduce levels of lung MMP-9. Furthermore, in a "disease" model, the compound did not affect cellular inflammation but did significantly reduce elastase-induced experimental emphysema. In summary, these data demonstrate for the first time that MMPs do not play a role in the increase in inflammatory mediators or cellular burden observed in these preclinical models. However, they do appear to be involved in the elastase-driven breakdown of airway structure, which is not due to a direct effect of the stimulus.

Address correspondence to: Professor Maria G. Belvisi, Head Respiratory Pharmacology Group, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK. E-mail: m.belvisi{at}imperial.ac.uk

This article has been cited by other articles:

				J. L. Wright, M. Cosio, and A. Churg Animal models of chronic obstructive pulmonary disease Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L1 - L15. [Abstract] [Full Text] [PDF]