Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling

Sabatini, Federica; Silvestri, Michela; Sale, Rosa; Serpero, Laura D.; Giuliani, Massimo; Scarso, Lucia; Favini, P.; Rossi, Giovanni A.

doi:10.1016/s1094-5539(03)00068-3

Cited by 30 publications

(33 citation statements)

References 40 publications

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“…Although viral replication was not influenced by MF, addition of MF during infection caused a marked (greater than fourfold) decrease in the release of both mediators. This finding supports data showing that GCS can reduce production of chemokines and cytokines following cellular activation [Wang et al, 1999;Papi et al, 2000;Suzuki et al, 2000;Sabatini et al, 2003]. It implies that GCS may reduce inflammation without detrimental effects on virus replication.…”

Section: Discussionsupporting

confidence: 90%

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Ghildyal

Dagher

Donninger

et al. 2005

Journal of Medical Virology

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The events linking rhinovirus (RV) infection to airway symptoms are poorly understood. The virus initially infects airway epithelium followed by a vigorous inflammatory response that may entail spread of RV from epithelium to other cells in the airway wall. However, RV has fastidious growth characteristics and to date reproductive infection of primary cells other than human airway epithelium has not been confirmed. Airway fibroblasts are adjacent to and in contact with epithelial cells, play a key role in innate immune responses, and may participate in the evolution of inflammation. To investigate fibroblast actions, we first determined whether RV could infect and replicate in primary culture human lung fibroblasts. RV serotype 16 (RV16) was used to infect fibroblasts grown from lung tissue, and virus infection with replication was demonstrated by a combination of techniques. RT-PCR was used to show an increase in RV transcription; confocal microscopy demonstrated colocalization of the replicative form of RV genome (double-stranded RNA) and RV16 proteins; infectious virus was also recovered from the culture supernatant of infected fibroblasts. Functional consequences of RV infection were next examined. RV infection of fibroblasts was followed by an increase in epithelial neutrophil-activating peptide-78 (ENA-78) mRNA and protein. The permeability factor vascular endothelial growth factor (VEGF) was also induced over a similar time course. These data suggest that interactions between RV and human fibroblasts are feasible, may coordinate neutrophil chemoattraction with enhanced vascular permeability and that fibroblasts may contribute to inflammatory responses following RV infections.

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Section: Discussionsupporting

confidence: 90%

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Ghildyal

Dagher

Donninger

et al. 2005

Journal of Medical Virology

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“…Also, we have shown for the first time that dexamethasone affected primary EBF growth in a dose-dependent manner: at concentrations less than 1 mM dexamethasone moderately enhanced cell proliferation while high concentrations greater than 10 mM suppressed cell proliferation, suggesting that the drug regulates cell growth in two ways in agreement with previous studies in corneal epithelial cells and dermal fibroblasts (Blumenkranz et al, 1984;Bourcier et al, 2000). Glucocorticoids at high concentrations inhibit cell division (Guerriero and Florini, 1980) and activity of fibroblast growth factors (Sabatini et al, 2003, Shull et al, 1995 or induce cell apoptosis and necrosis (Bourcier et al, 2000;Chen et al, 2006). Our data were also consistent with those from Kraft et al (2001) and Pickholtz et al (2011) that dexamethasone at low concentrations stimulated EBF proliferation, implying that dexamethasone has a mitogenic effect at low doses similar to physiological conditions.…”

Section: Discussionsupporting

confidence: 89%

“…Glucocorticoids are also important drugs to treat airway inflammation and have generally been controversially considered to have anti-fibrotic effects to limit airway remodelling (Goulet et al, 2007;Ward and Walters, 2005). In some studies in fibroblasts in vitro, these drugs enhanced fibroblast proliferation (Fouty et al, 2006) and in some they inhibit cell proliferation and the release of fibrotic factors (Sabatini et al, 2003;Wen et al, 2003). Bronchodilation is induced via activation of the β 2 -adrenoceptor systems by the β 2 -agonists; however, long-term usage of these drugs, e.g., the long-acting clenbuterol, results in receptor desensitization and downregulation in vivo (Abraham et al, 2002;Brodde et al, 1985) and might enhance disease morbidity.…”

Section: Introductionmentioning

confidence: 99%

Concomitant inhibition of primary equine bronchial fibroblast proliferation and differentiation by selective β2-adrenoceptor agonists and dexamethasone

Franke

Abraham

2014

European Journal of Pharmacology

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“…Introduction of salmeterol into the airways of asthmatics has been found to reduce IL-8 and myeloperoxidase levels in bronchoalveolar lavage fluid; in the same study, high-dose inhaled corticosteroid treatment increased rather than decreased airway neutrophils [23]. However, in vitro studies have suggested that there are dose-dependent effects of fluticasone on the inhibition of IL-8 and other mediators released from various types of cells, including airway epithelial cells [24], smooth muscle cells [25] and fibroblasts [26]. A synergistic effect of SFP on the inhibition of mediator release has also been demonstrated [27][28][29][30].…”

Section: Discussionmentioning

confidence: 88%

Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD

Dw¹,

Cw²,

Kc³

et al. 2009

Eur Respir J

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The anti-inflammatory effects of salmeterol/fluticasone (SFP), tiotropium/fluticasone (Tio+FP) and tiotropium (Tio) alone were investigated on the inflammatory cells and mediators in sputum induced from chronic obstructive pulmonary disease patients.Subjects were either newly diagnosed or had not taken any medication for 3 months prior to the study. Subjects (n599) were randomised (not double blinded) and received either SFP (100/ 1,000 mg daily), Tio+FP (18/1,000 mg daily) or Tio (18 mg daily) for 12 weeks. Induced sputum and serum C-reactive protein (CRP) were analysed prior to and at the end of treatment.The results showed that treatment with SFP caused a significant reduction in interleukin (IL)-8 and matrix metalloprotease (MMP)-9 in induced sputum, compared with treatment with Tio alone. There were no treatment differences between the SFP and Tio+FP groups in decreasing IL-8 and MMP-9 levels. The reduction in IL-8 showed significant association with the reduction in MMP-9. All treatment groups failed to significantly reduce the numbers of total cells, neutrophils, macrophages and eosinophils in induced sputum; in addition, there were no treatment differences in terms of improvement of forced expiratory volume in one second, forced vital capacity, CRP or quality of life between the three groups.The anti-inflammatory effects of salmeterol/fluticasone probably contribute to the clinical benefits seen in chronic obstructive pulmonary disease patients.

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Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling

Cited by 30 publications

References 40 publications

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Concomitant inhibition of primary equine bronchial fibroblast proliferation and differentiation by selective β2-adrenoceptor agonists and dexamethasone

Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD

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