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
✍ Scribed by Girolamo Pelaia; Luca Gallelli; Bruno D'Agostino; Alessandro Vatrella; Giovanni Cuda; Donatella Fratto; Teresa Renda; Umberto Galderisi; Elena Piegari; Nunzio Crimi; Francesco Rossi; Mario Caputi; Francesco S. Costanzo; Carlo Vancheri; Rosario Maselli; Serafino A. Marsico
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 241 KB
- Volume
- 210
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
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 [^3^H]‐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.