Fluticasone inhibits the progression of allergen‐induced structural airway changes

Vanacker, Nele J.; Palmans, Els; Pauwels, Romain; Kips, Johan

doi:10.1046/j.1365-2222.2002.01394.x

Cited by 30 publications

(20 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported in children with asthma that 6 weeks treatment with budesonide plus formoterol did not further reduce circulating procollagen levels compared to budesonide (Heuck et al, 2000). In a murine allergen-induced model of airway remodeling, the combination of fluticasone and salmeterol over a period of 2 weeks significantly increased fibronectin and collagen in the airway wall compared to placebo or fluticasone (Vanacker et al, 2002). These observations imply that under chronic inflammation, adding LABA to corticosteroids does not further reduce the remodeling process in the lung.…”

Section: Discussionmentioning

confidence: 89%

Opposite effect of corticosteroids and long‐acting β₂‐agonists on serum‐ and TGF‐β₁‐induced extracellular matrix deposition by primary human lung fibroblasts

Goulet

Bihl

Gambazzi

et al. 2006

Journal Cellular Physiology

View full text Add to dashboard Cite

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation and major structural lung tissue changes including increased extracellular matrix (ECM) deposition. Inhaled corticosteroids and long-acting b 2 -agonists (LABA) are the basic treatment for both diseases, but their effect on airway remodeling remains unclear. In this study, we investigated the effect of corticosteroids and LABA, alone or in combination, on total ECM and collagen deposition, gene expression, cell proliferation, and IL-6, IL-8, and TGF-b 1 levels by primary human lung fibroblasts. In our model, fibroblasts in 0.3% albumin represented a non-inflammatory condition and stimulation with 5% FCS and/or TGF-b 1 mimicked an inflammatory environment with activation of tissue repair. FCS (5%) increased total ECM, collagen deposition, cell proliferation, and IL-6, IL-8, and TGF-b 1 levels. In 0.3% albumin, corticosteroids reduced total ECM and collagen deposition, involving the glucocorticoid receptor (GR) and downregulation of collagen, heat shock protein 47 (Hsp47), and Fli1 mRNA expression. In 5% FCS, corticosteroids increased ECM deposition, involving upregulation of COL4A1 and CTGF mRNA expression. LABA reduced total ECM and collagen deposition under all conditions partly via the b 2 -adrenergic receptor. In combination, the drugs had an additive effect in the presence or absence of TGF-b 1 further decreasing ECM deposition in 0.3% albumin whereas counteracting each other in 5% FCS. These data suggest that the effect of corticosteroids, but not of LABA, on ECM deposition by fibroblasts is altered by serum. These findings imply that as soon as airway inflammation is resolved, long-term treatment with combined drugs may beneficially reduce pathological tissue remodeling.

show abstract

Section: Discussionmentioning

confidence: 89%

Opposite effect of corticosteroids and long‐acting β₂‐agonists on serum‐ and TGF‐β₁‐induced extracellular matrix deposition by primary human lung fibroblasts

Goulet

Bihl

Gambazzi

et al. 2006

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…However, fluticasone administered after allergen exposure failed to reverse established airway structural changes in these rats. In this rat model, when OVA exposure is increased by an additional 2 weeks, enhanced airway collagen deposition is observed [43]. Treatment with fluticasone during this last 2 weeks of allergen challenge inhibits the additional increase in collagen deposition [43].…”

Section: Discussionmentioning

confidence: 91%

“…In this rat model, when OVA exposure is increased by an additional 2 weeks, enhanced airway collagen deposition is observed [43]. Treatment with fluticasone during this last 2 weeks of allergen challenge inhibits the additional increase in collagen deposition [43]. It is of interest that combining salmeterol with fluticasone during the last 2 weeks of this rat asthma model results in increased airway wall thickness and deposition of collagen and fibronection in the lungs [44].…”

Section: Discussionmentioning

confidence: 98%

Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone

Pe¹,

Jonas²,

Tsai³

et al. 2004

European Respiratory Journal

View full text Add to dashboard Cite

Lung expression of the extracellular matrix protein, laminin, and its receptor, laminin-1 receptor, were examined in a mouse model of asthma with airway remodelling.Ovalbumin (OVA) was administered to BALB/c mice, intraperitoneally on days 0 and 14, and intranasally periodically between days 14 and 75.The mice developed airway eosinophil and mononuclear inflammatory cell infiltration and fibrosis. On day 76, a marked increase in total laminin was seen in the airways of OVA-treated mice compared to controls by Western blot analysis. The increased laminin expression was detected immunocytochemically in the thickened subepithelial basement membrane and around airways and blood vessels. The OVA-treated mice showed increased expression of the a1, b1, and c1 chains of the laminin-1 isoform in monocytes, macrophages and eosinophils infiltrating the airways. Laminin-1 receptor expression was increased in inflammatory and endothelial cells in the lungs of OVAtreated mice compared to controls. Treatment of OVA-sensitised/challenged mice with dexamethasone reduced airway expression of laminin and laminin-1 receptor in OVAtreated mice but not airway hyperresponsiveness to methacholine.Laminin deposition may be an important component of the airway remodelling observed in chronic allergic lung inflammation and is a process modulated by corticosteroids.

show abstract

“…These structural changes can affect AHR in human asthma (41). In murine asthma models, chronic OVA exposure and associated airway remodeling has been reported to cause a progressive decrease in AHR (22,42,43). We did not assess airway remodeling in the current study because few of the aforementioned airway remodeling features would have manifested by d45.…”

Section: Original Researchmentioning

confidence: 99%

Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model

Chen¹,

Hegde

Choi

et al. 2015

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

b-Arrestin-2 (barr2) is a ubiquitously expressed cytosolic protein that terminates G protein-coupled receptor signaling and transduces G protein-independent signaling. We previously showed that mice lacking barr2 do not develop an asthma phenotype when sensitized to, and challenged with, allergens. The current study evaluates if an established asthma phenotype can be mitigated by deletion of barr2 using an inducible Cre recombinase. We sensitized and challenged mice to ovalbumin (OVA) and demonstrated that on Day (d) 24 the allergic asthma phenotype was apparent in uninduced barr2 and wild-type (WT) mice. In a second group of OVA-treated mice, tamoxifen was injected on d24 to d28 to activate Cre recombinase, and OVA aerosol challenge was continued through d44. The asthma phenotype was assessed using lung mechanics measurements, bronchoalveolar lavage cell analysis, and histological assessment of mucin and airway inflammation. Compared with their respective saline-treated controls, OVA-treated WT mice and mice expressing the inducible Cre recombinase displayed a significant asthma phenotype at d45. Whereas tamoxifen treatment had no significant effect on the asthma phenotype in WT mice, it inhibited barr2 expression and caused a significant reduction in airway hyperresponsiveness (AHR) in Cre-inducible mice. These findings suggest that barr2 is actively required for perpetuation of the AHR component of the allergic asthma phenotype. Our finding that barr2 participates in the perpetuation of AHR in an asthma model means that targeting barr2 may provide immediate and potentially longterm relief from daily asthma symptoms due to AHR irrespective of inflammation.

show abstract

Fluticasone inhibits the progression of allergen‐induced structural airway changes

Abstract: The progression of established allergen-induced structural airway changes in sensitized rats can be inhibited by treatment with fluticasone.

Cited by 30 publications

References 30 publications

Opposite effect of corticosteroids and long‐acting β₂‐agonists on serum‐ and TGF‐β₁‐induced extracellular matrix deposition by primary human lung fibroblasts

Opposite effect of corticosteroids and long‐acting β₂‐agonists on serum‐ and TGF‐β₁‐induced extracellular matrix deposition by primary human lung fibroblasts

Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone

Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model

Contact Info

Product

Resources

About

Fluticasone inhibits the progression of allergen‐induced structural airway changes

Abstract: The progression of established allergen-induced structural airway changes in sensitized rats can be inhibited by treatment with fluticasone.

Cited by 30 publications

References 30 publications

Opposite effect of corticosteroids and long‐acting β2‐agonists on serum‐ and TGF‐β1‐induced extracellular matrix deposition by primary human lung fibroblasts

Opposite effect of corticosteroids and long‐acting β2‐agonists on serum‐ and TGF‐β1‐induced extracellular matrix deposition by primary human lung fibroblasts

Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone

Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model

Contact Info

Product

Resources

About

Opposite effect of corticosteroids and long‐acting β₂‐agonists on serum‐ and TGF‐β₁‐induced extracellular matrix deposition by primary human lung fibroblasts

Opposite effect of corticosteroids and long‐acting β₂‐agonists on serum‐ and TGF‐β₁‐induced extracellular matrix deposition by primary human lung fibroblasts