title: Effects of triamcinolone acetonide on adult human lung fibroblasts: decrease in proliferation, surface molecule expression and mediator release.
abstract: BACKGROUND
  Lung fibroblasts may have a pivotal role in airway inflammation as they are involved in continuous cycles of mediator secretion, proliferation, activation and cross-talk with recruited inflammatory cells. The role of fibroblasts as intermediate participants in the inflammatory network suggests that they could represent an important target for drugs commonly used in asthma; thus, we investigated the effects of triamcinolone acetonide (TAA) on primary human lung fibroblasts.
  
  
  METHODS
  The in vitro activity of increasing concentrations (10(-9) to 10(-7) M) of TAA in fibroblast cultures was evaluated as regards the following parameters: proliferation, extracellular matrix (ECM) release, cytokine/chemokine secretion and surface antigen expression.
  
  
  RESULTS
  All concentrations of TAA decreased fetal calf serum (FCS)-induced fibroblast proliferation, whereas in the presence of FCS plus basic fibroblast growth factor TAA was only effective at 10(-8) and 10(-7) M. TAA failed to decrease ECM, whereas at 10(-8) and 10(-7) M it decreased IL-6 and IL-8 secretion to different extents. In the presence of IFN-gamma the drug was able to reduce VCAM-1 expression at all of the tested concentrations; on the other hand, in TGF-beta 1-driven cultures a decrease in CD54 expression was detected with TAA at 10(-8) and 10(-7) M.
  
  
  CONCLUSIONS
  TAA acts on some functional properties of human lung fibroblasts that make these cells active participants in the inflammatory network. The ability of TAA to inhibit lung fibroblast proliferation may prevent or even reverse some of the histological changes that characterize airway remodeling in chronic inflammatory diseases; moreover, IL-6, IL-8 and surface molecule decreases by TAA may suggest a direct anti-inflammatory effect of the drug by suppression of resident lung cell function.
authors.affiliation: Allergy and Respiratory Diseases Service, University of Genoa, Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Oddera
authors.forename: F
authors.initials: F
authors.lastname: Cagnoni
authors.forename: S
authors.initials: S
authors.lastname: Mangraviti
authors.forename: J
authors.initials: J
authors.lastname: Giron-Michel
authors.forename: O
authors.initials: O
authors.lastname: Popova
authors.forename: G W
authors.initials: GW
authors.lastname: Canonica
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003094:Collagen / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism; D005938:Glucocorticoids / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014222:Triamcinolone Acetonide / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology
chemical_list: D005353:Fibronectins; D005938:Glucocorticoids; D015850:Interleukin-6; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D003094:Collagen; D014222:Triamcinolone Acetonide