Inhibition of MMP-9 expression by PPARgamma activators in human bronchial epithelial cells.
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)-alpha, 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 (PPARgamma) might modulate MMP-9 expression in two different bronchial epithelial cell lines.


RESULTS
PPARgamma was expressed and was functionally active in NL20 and BEAS cells. Activation of PPARgamma by rosiglitazone or pioglitazone significantly reduced TNF-alpha 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 PPARgamma which resulted from the inhibition of NF-kappaB activation in these cells, as determined by transient transfection assays and electromobility shift assays.


CONCLUSIONS
Activation of PPARgamma 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.
Hetzel
M
M
Department of Internal Medicine II, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany. martin.hetzel@medizin.uni-ulm.de
Walcher
D
D
Grüb
M
M
Bach
H
H
Hombach
V
V
Marx
N
N
D015152:Blotting, Northern; D001980:Bronchi / Q000378:metabolism*; D001991:Bronchitis / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D000077205:Pioglitazone; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D007004:Hypoglycemic Agents; D061965:Matrix Metalloproteinase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D019715:Tissue Inhibitor of Metalloproteinase-1; D014157:Transcription Factors; D000077154:Rosiglitazone; D020780:Matrix Metalloproteinase 9; D000077205:Pioglitazone