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Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors.
Life Sci. 2004 Jul 02; 75(7):823-40.LS

Abstract

Over-expression of matrix metalloproteinases by lung fibroblasts has been blamed for much of the tissue destruction associated with airway inflammation. Because cyclic AMP is known to regulate fibroblast proliferation, as well as cytokine and extracellular matrix protein production, the current study was designed to evaluate the ability of three selective phosphodiesterase (PDE) type 4 inhibitors, rolipram, cilomilast and CI-1044, to inhibit extracellular matrix degradation. Using zymography and ELISA, we found that pro-MMP-2 release was enhanced following 24 h treatment of human lung fibroblast (MRC-5) with TGF-beta1 (10 ng/ml) or TNF-alpha (10 ng/ml), whereas PMA (0.02 microM) had no effect. One hour of pre-incubation with PDE4 inhibitors (10 microM) induced an inhibition of TNF-alpha-stimulated pro-MMP-2 release. Zymography and immunoblotting revealed that fibroblasts cultured with PMA or TNF-alpha released increased amounts of pro-MMP-1, whereas TGF-beta1 had no effect. Incubation with CI-1044 or cilomilast significantly prevented the TNF-alpha increase in pro-MMP-1. These results suggest that PDE4 inhibitors are effective in inhibiting the pro-MMP-2 and pro-MMP-1 secretion induced by TNF-alpha and might underline a potential therapeutic benefit of selective PDE4 inhibitors in lung diseases associated with abnormal tissue remodelling.

Authors+Show Affiliations

INSERM U456, Université de Rennes 1, 2 avenue du Pr Léon Bernard, 35043 Rennes, France. corinne.chouly@rennes.inserm.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15183075

Citation

Martin-Chouly, Corinne A E., et al. "Modulation of Matrix Metalloproteinase Production From Human Lung Fibroblasts By Type 4 Phosphodiesterase Inhibitors." Life Sciences, vol. 75, no. 7, 2004, pp. 823-40.
Martin-Chouly CA, Astier A, Jacob C, et al. Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors. Life Sci. 2004;75(7):823-40.
Martin-Chouly, C. A., Astier, A., Jacob, C., Pruniaux, M. P., Bertrand, C., & Lagente, V. (2004). Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors. Life Sciences, 75(7), 823-40.
Martin-Chouly CA, et al. Modulation of Matrix Metalloproteinase Production From Human Lung Fibroblasts By Type 4 Phosphodiesterase Inhibitors. Life Sci. 2004 Jul 2;75(7):823-40. PubMed PMID: 15183075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors. AU - Martin-Chouly,Corinne A E, AU - Astier,Alexandra, AU - Jacob,Claire, AU - Pruniaux,Marie-Pierre, AU - Bertrand,Claude, AU - Lagente,Vincent, PY - 2003/07/01/received PY - 2004/01/12/accepted PY - 2004/6/9/pubmed PY - 2004/7/21/medline PY - 2004/6/9/entrez SP - 823 EP - 40 JF - Life sciences JO - Life Sci VL - 75 IS - 7 N2 - Over-expression of matrix metalloproteinases by lung fibroblasts has been blamed for much of the tissue destruction associated with airway inflammation. Because cyclic AMP is known to regulate fibroblast proliferation, as well as cytokine and extracellular matrix protein production, the current study was designed to evaluate the ability of three selective phosphodiesterase (PDE) type 4 inhibitors, rolipram, cilomilast and CI-1044, to inhibit extracellular matrix degradation. Using zymography and ELISA, we found that pro-MMP-2 release was enhanced following 24 h treatment of human lung fibroblast (MRC-5) with TGF-beta1 (10 ng/ml) or TNF-alpha (10 ng/ml), whereas PMA (0.02 microM) had no effect. One hour of pre-incubation with PDE4 inhibitors (10 microM) induced an inhibition of TNF-alpha-stimulated pro-MMP-2 release. Zymography and immunoblotting revealed that fibroblasts cultured with PMA or TNF-alpha released increased amounts of pro-MMP-1, whereas TGF-beta1 had no effect. Incubation with CI-1044 or cilomilast significantly prevented the TNF-alpha increase in pro-MMP-1. These results suggest that PDE4 inhibitors are effective in inhibiting the pro-MMP-2 and pro-MMP-1 secretion induced by TNF-alpha and might underline a potential therapeutic benefit of selective PDE4 inhibitors in lung diseases associated with abnormal tissue remodelling. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/15183075/Modulation_of_matrix_metalloproteinase_production_from_human_lung_fibroblasts_by_type_4_phosphodiesterase_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024320504003273 DB - PRIME DP - Unbound Medicine ER -