AIRWAY BIOLOGY

Inhibition of MMP-9 expression by PPAR activators in human bronchial epithelial cells

M Hetzel, D Walcher, M Grüb, H Bach, V Hombach, N Marx

Department of Internal Medicine II, University of Ulm, Germany

Correspondence to:
Correspondence to:
Dr M Hetzel, Department of Internal Medicine II, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany;
martin.hetzel{at}medizin.uni-ulm.de

Background: The release of matrix degrading enzymes such as matrix metalloproteinase 9 (MMP-9) from bronchial epithelial cells is critically involved in airway wall remodelling in chronic inflammatory processes of the respiratory system. MMP-9 expression is induced by inflammatory mediators such as tumour necrosis factor (TNF)-, but to date nothing is known about the mechanisms of inhibition of MMP-9 expression in these cells.

Methods: A study was undertaken to examine whether activators of the nuclear transcription factor peroxisome proliferator activated receptor gamma (PPAR) might modulate MMP-9 expression in two different bronchial epithelial cell lines.

Results: PPAR was expressed and was functionally active in NL20 and BEAS cells. Activation of PPAR by rosiglitazone or pioglitazone significantly reduced TNF- and PMA induced MMP-9 gelatinolytic activity in a concentration dependent manner in both cell lines, but did not alter the expression of tissue inhibitor of MMPs type 1 (TIMP-1), the local inhibitor of MMP-9. Northern blot analysis revealed a decrease in MMP-9 mRNA expression following treatment with PPAR which resulted from the inhibition of NF-B activation in these cells, as determined by transient transfection assays and electromobility shift assays.

Conclusion: Activation of PPAR in human bronchial epithelial cells limits the expression of matrix degrading MMP-9. This might have therapeutic applications in chronic inflammatory processes of the respiratory system.

Keywords: matrix metalloproteinase (MMP)-9; peroxisome proliferator activated receptor (PPAR)

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