RESUMO
PURPOSE: Fibroblast growth factor 2 (FGF2) has been shown to inhibit airway inflammation, mucus production, and airway hyperresponsiveness in mouse model of asthma. The aim of this study was to evaluate the safety and efficacy of inhaled recombinant FGF2 in asthmatic patients. METHODS: Eight asthmatics were eligible for the study. All patients were admitted to a hospital, and recombinant FGF2 was administered using a nebulizer at a concentration of 4.5 ng/mL three times a day for one week. Pulmonary function test, methacholine bronchial provocation test, induced sputum analysis, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ) were performed at the beginning of wash-out period, before and after the treatment, and at the end of study. And all these parameters were compared before and after FGF2 treatment. RESULTS: There were no serious adverse events associated with recombinant FGF2 during five-week study period. Daytime and nocturnal symptoms improved after the treatment (P=0.028 and P=0.012, respectively). AQLQ and ACT also improved after the treatment (P=0.017 and P=0.011, respectively). However, lung function, airway hyperresponsiveness, and airway inflammation showed no significant difference before and after the treatment. CONCLUSION: Inhaled recombinant FGF2 was safely used to eight asthmatics without any serious adverse events, and improved daytime and nocturnal symptoms, and quality of life in adult asthmatics. FGF2 may be a potential drug in the treatment of asthma.
Assuntos
Adulto , Animais , Humanos , Camundongos , Remodelação das Vias Aéreas , Asma , Testes de Provocação Brônquica , Fator 2 de Crescimento de Fibroblastos , Inflamação , Pulmão , Cloreto de Metacolina , Muco , Nebulizadores e Vaporizadores , Projetos Piloto , Qualidade de Vida , Testes de Função Respiratória , Escarro , Inquéritos e QuestionáriosRESUMO
The fourth author's name was misprinted.
Assuntos
Humanos , Fator 2 de Crescimento de Fibroblastos , Projetos PilotoRESUMO
Increased expression of a number of proinflammatory genes, including IL-8, is associated with inflammatory conditions such as asthma. Glucocorticoid receptor (GR)beta, one of the GR isoforms, has been suggested to be upregulated in asthma associated with glucocorticoid insensitivity and to work as a dominant negative inhibitor of wild type GRalpha. However, recent data suggest that GRbeta is not a dominant negative inhibitor of GRalpha in the transrepressive process and has its own functional role. We investigated the functional role of GRbeta expression in the suppressive effect of glucocorticoids on tumor necrosis factor (TNF)-alpha-induced IL-8 release in an airway epithelial cell line. GRbeta expression was induced by treatment of epithelial cells with either dexamethasone or TNF-alpha. GRbeta was able to inhibit glucocorticoid-induced transcriptional activation mediated by binding to glucocorticoid response elements (GREs). The suppressive effect of dexamethasone on TNF-alpha-induced IL-8 transcription was not affected by GRbeta overexpression, rather GRbeta had its own weak suppressive activity on TNF-alpha-induced IL-8 expression. Overall histone deacetylase activity and histone acetyltransferase activity were not changed by GRbeta overexpression, but TNF-alpha-induced histone H4 acetylation at the IL-8 promoter was decreased with GRbeta overexpression. This study suggests that GRbeta overexpression does not affect glucocorticoid-induced suppression of IL-8 expression in airway epithelial cells and GRbeta induces its own histone deacetylase activity around IL-8 promoter site.
Assuntos
Humanos , Acetilação , Linhagem Celular Tumoral , Dexametasona/farmacologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Histonas/metabolismo , Interleucina-8/genética , Receptores de Glucocorticoides/genética , Ativação Transcricional , Transfecção , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Increased expression of a number of proinflammatory genes, including IL-8, is associated with inflammatory conditions such as asthma. Glucocorticoid receptor (GR)beta, one of the GR isoforms, has been suggested to be upregulated in asthma associated with glucocorticoid insensitivity and to work as a dominant negative inhibitor of wild type GRalpha. However, recent data suggest that GRbeta is not a dominant negative inhibitor of GRalpha in the transrepressive process and has its own functional role. We investigated the functional role of GRbeta expression in the suppressive effect of glucocorticoids on tumor necrosis factor (TNF)-alpha-induced IL-8 release in an airway epithelial cell line. GRbeta expression was induced by treatment of epithelial cells with either dexamethasone or TNF-alpha. GRbeta was able to inhibit glucocorticoid-induced transcriptional activation mediated by binding to glucocorticoid response elements (GREs). The suppressive effect of dexamethasone on TNF-alpha-induced IL-8 transcription was not affected by GRbeta overexpression, rather GRbeta had its own weak suppressive activity on TNF-alpha-induced IL-8 expression. Overall histone deacetylase activity and histone acetyltransferase activity were not changed by GRbeta overexpression, but TNF-alpha-induced histone H4 acetylation at the IL-8 promoter was decreased with GRbeta overexpression. This study suggests that GRbeta overexpression does not affect glucocorticoid-induced suppression of IL-8 expression in airway epithelial cells and GRbeta induces its own histone deacetylase activity around IL-8 promoter site.