Endothelin-1 induces proliferation of human lung fibroblasts and IL-11 secretion through an ET(A) receptor-dependent activation of MAP kinases
| Autor: | Luca Gallelli, Marilisa De Nardo, Carlo Vancheri, Francesco Costanzo, Mario Caputi, Mauro Maniscalco, Giovanni Cuda, Bruno D'Agostino, V. Gioffrè, C. Mastruzzo, Serafino A. Marsico, Matteo Sofia, Francesco Rossi, Girolamo Pelaia, Alessandro Vatrella, Umberto Galderisi, Elisa Trovato Salinaro, Nunzio Crimi, Rosario Maselli, D. Fratto |
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| Přispěvatelé: | Gallelli, Luca, Pelaia, Girolamo, D'Agostino, Bruno, Cuda, Giovanni, Vatrella, Alessandro, Fratto, Donatella, Gioffrè, Vincenza, Galderisi, Umberto, De Nardo, Marilisa, Mastruzzo, Claudio, Salinaro, Elisa Trovato, Maniscalco, Mauro, Sofia, Matteo, Crimi, Nunzio, Rossi, Francesco, Caputi, Mario, Costanzo, Francesco S, Maselli, Rosario, Marsico, Serafino A, Vancheri, Carlo, Gallelli, L, Pelaia, G, Cuda, G, Vatrella, A, Fratto, D, Gioffre, V, DE NARDO, M, Mastruzzo, C, Salinaro, Et, Maniscalco, M, Sofia, M, Crimi, N, Rossi, F, Caputi, M, Costanzo, F, Maselli, R, Marsico, Sa, Vancheri, C. |
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Time Factors Cell Survival Endothelin A Receptor Antagonists Biology Mitogen-Activated Protein Kinase Biochemistry Endothelin B Receptor Antagonist Humans Secretion RNA Messenger Phosphorylation Receptor Molecular Biology Lung Cell Proliferation IL-6 Endothelin-1 Kinase Cell growth Interleukin-6 lung fibroblasts Cell Biology ET-1 receptors Fibroblasts Interleukin-11 Receptor Endothelin A Endothelin 1 MAPK Receptor Endothelin B ET-1 Cell biology Endothelin B Receptor Antagonists Intracellular signal transduction IL-11 Cell culture Fibroblast Mitogen-Activated Protein Kinases Endothelin A Receptor Antagonist Human |
| Zdroj: | Journal of cellular biochemistry. 96(4) |
| ISSN: | 0730-2312 |
| Popis: | Endothelin-1 (ET-1) is implicated in the fibrotic responses characterizing interstitial lung diseases, as well as in the airway remodeling process occurring in asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal human lung fibroblasts (NHLFs), the ET-1 receptor subtypes, and the intracellular signal transduction pathways involved in the proliferative effects of this peptide. Therefore, cells were exposed to ET-1 in the presence or absence of an overnight pre-treatment with either ETA or ETB selective receptor antagonists. After cell lysis, immunoblotting was performed using monoclonal antibodies against the phosphorylated, active forms of mitogen-activated protein kinases (MAPK). ET-1 induced a significant increase in MAPK phosphorylation pattern, and also stimulated fibroblast proliferation and IL-6/IL-11 release into cell culture supernatants. All these effects were inhibited by the selective ETA antagonist BQ-123, but not by the specific ETB antagonist BQ-788. The stimulatory influence of ET-1 on IL-11, but not on IL-6 secretion, was prevented by MAPK inhibitors. Therefore, such results suggest that in human lung fibroblasts ET-1 exerts a profibrogenic action via an ETA receptor-dependent, MAPK-mediated induction of IL-11 release and cell proliferation. © 2005 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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