Girolamo Pelaia and Luca Gallelli contributed equally to the work presented in this article.
Effects of TGF-β and glucocorticoids on map kinase phosphorylation, IL-6/IL-11 secretion and cell proliferation in primary cultures of human lung fibroblasts†
Article first published online: 16 OCT 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 210, Issue 2, pages 489–497, February 2007
How to Cite
Pelaia, G., Gallelli, L., D'Agostino, B., Vatrella, A., Cuda, G., Fratto, D., Renda, T., Galderisi, U., Piegari, E., Crimi, N., Rossi, F., Caputi, M., Costanzo, F. S., Vancheri, C., Maselli, R. and Marsico, S. A. (2007), Effects of TGF-β and glucocorticoids on map kinase phosphorylation, IL-6/IL-11 secretion and cell proliferation in primary cultures of human lung fibroblasts. J. Cell. Physiol., 210: 489–497. doi: 10.1002/jcp.20884
- Issue published online: 22 NOV 2006
- Article first published online: 16 OCT 2006
- Manuscript Accepted: 22 AUG 2006
- Manuscript Received: 17 MAR 2006
Transforming growth factor-β1 (TGF-β1) is crucially involved in the fibrotic events characterizing interstitial lung diseases (ILDs), as well as in the airway remodeling process typical of asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal and fibrotic human lung fibroblasts (HLFs), the effects of TGF-β1 on mitogen-activated protein kinase (MAPK) phosphorylation, cell proliferation, and production of interleukins 6 (IL-6) and 11 (IL-11), in the presence or absence of a pretreatment with budesonide (BUD). MAPK phosphorylation was detected by Western blotting, cell viability and proliferation were evaluated using Trypan blue staining and [3H]-thymidine incorporation assay, respectively, and the release of IL-6 and IL-11 into cell culture supernatants was assessed by ELISA. TGF-β1 (10 ng/ml) significantly stimulated MAPK phosphorylation (P < 0.01), and also enhanced cell proliferation as well as the secretion of both IL-6 and IL-11, which reached the highest increases at the 72nd h of cell exposure to this growth factor. All such effects were prevented by BUD (10−8 M) and, with the exception of IL-6 release, also by a mixture of MAPK inhibitors. Therefore, our findings suggest that the fibrotic action exerted by TGF-β1 in the lung is mediated at least in part by MAPK activation and by an increased synthesis of the profibrogenic cytokines IL-6 and IL-11; all these effects appear to be prevented by corticosteroids via inhibition of MAPK phosphorylation. J. Cell. Physiol. 210: 489–497, 2007. © 2006 Wiley-Liss, Inc.