Abstract | BACKGROUND: AIM: To evaluate whether ciclesonide could directly modulate in vitro bronchial fibroblast functions being converted into des-ciclesonide by these pluripotent cells involved in the regulation of airway inflammation and remodelling. METHODS: RESULTS: The presence of ciclesonide in cell cultures induced a significant downregulation of: (a) bFGF-induced fibroblast proliferation and TNF-alpha-induced ICAM-1 expression, at the 0.3-9.0 microM concentrations (p<0.05); (b) TNF-alpha-induced MCP-1 release, at all the concentrations tested (p<0.05); (c) TNF-alpha-induced eotaxin release, at the three highest concentrations (0.9-9.0 microM) (p<0.05); (d) TGF-beta1-induced of alpha-SMA protein expression at the 0.3-3.0 microM concentrations, associated with a reduction in the organization of alpha-SMA stress fibres. CONCLUSIONS: These data show at cellular level an effective anti-inflammatory activity of ciclesonide on human lung fibroblasts and support the hypothesis that also these cells, in addition to airway epithelial cells, may be involved in converting the parental compound into its active metabolite in the airways.
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Authors | Silvia Boero, Federica Sabatini, Michela Silvestri, Loredana Petecchia, Antonio Nachira, Annalisa Pezzolo, Lucia Scarso, Giovanni A Rossi |
Journal | Immunology letters
(Immunol Lett)
Vol. 112
Issue 1
Pg. 39-46
(Sep 15 2007)
ISSN: 0165-2478 [Print] Netherlands |
PMID | 17707916
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Actins
- Anti-Asthmatic Agents
- Anti-Inflammatory Agents
- CCL11 protein, human
- CCL2 protein, human
- Chemokine CCL11
- Chemokine CCL2
- Chemokines, CC
- Pregnenediones
- Transforming Growth Factor beta1
- Tumor Necrosis Factor-alpha
- Fibroblast Growth Factor 2
- Intercellular Adhesion Molecule-1
- desisobutyrylciclesonide
- ciclesonide
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Topics |
- Actins
(metabolism)
- Anti-Asthmatic Agents
(metabolism, pharmacology)
- Anti-Inflammatory Agents
(metabolism, pharmacology)
- Biotransformation
- Cell Differentiation
(drug effects)
- Cell Line
- Cell Proliferation
(drug effects)
- Chemokine CCL11
- Chemokine CCL2
(metabolism)
- Chemokines, CC
(metabolism)
- Dose-Response Relationship, Drug
- Fibroblast Growth Factor 2
(metabolism)
- Fibroblasts
(drug effects, metabolism)
- Humans
- Intercellular Adhesion Molecule-1
(metabolism)
- Lung
(cytology, drug effects, metabolism)
- Pregnenediones
(metabolism, pharmacology)
- Stress Fibers
(drug effects, metabolism)
- Transforming Growth Factor beta1
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
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