Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tissue destruction, resulting in emphysema, can be a consequence of several pathologic processes. The current study evaluated the effects of the phosphodiesterase (PDE)4 inhibitor, cilomilast, and other PDE inhibitors on the ability of fibroblasts to degrade extracellular matrix. Using the three-dimensional collagen gel culture system, fibroblasts (HFL-1) were cultured with tumor necrosis factor (TNF)-alpha, known to induce matrix metalloproteinase (MMP) release, and/or neutrophil elastase (NE), which can induce MMP activation. On Day 4, gels containing TNF-alpha and NE were significantly degraded (20.8 +/- 2.9% of original collagen content). Cilomilast (10 micro M) inhibited this degradation (84.4 +/- 8.4%).
Amrinone
, a PDE3 inhibitor, and zaprinast, a PDE5 inhibitor, had no effect. Gelatin zymography and immunoblotting revealed that fibroblasts cultured with TNF-alpha released increased amounts of latent
MMP-1
and -9. The addition of NE resulted in the conversion of
MMP-1
and -9 to their active forms, indicative of collagen degradation. Cilomilast inhibited the release of
MMP-1
and -9, as well as conversion of
MMP-1
to its active form. Using real-time PCR analysis, cilomilast's effect on
MMP-1
release was not associated with the proteinase's mRNA expression, suggesting that the inhibition of release is regulated at the post-transcriptional level. These results suggest that cilomilast may be a potentially effective therapeutic agent in diseases characterized by excessive tissue destruction, such as emphysema.
...
PMID:Phosphodiesterase 4 inhibitor cilomilast inhibits fibroblast-mediated collagen gel degradation induced by tumor necrosis factor-alpha and neutrophil elastase. 1235 83
