The effect of glucocorticoids on proliferation of human cultured airway smooth muscle

Stewart, Alastair G.; Fernandes, Darren; Tomlinson, Paul R.

doi:10.1111/j.1476-5381.1995.tb15127.x

Cited by 103 publications

(90 citation statements)

References 45 publications

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“…In addition to their anti-inflammatory effects, gluco-corticosteroids may inhibit ASM remodeling as shown in an animal model of chronic allergic asthma (Bos et al, 2007). In line with these findings, in vitro studies have indicated that glucocorticosteroids inhibit ASM cell proliferation (Stewart et al, 1995;Fernandes et al, 1999;Roth et al, 2002). In ASM cells, glucocorticosteroids accelerate the nuclear translocation of the glucocorticosteroid receptor and CCAAT/enhancer binding protein ␣ (C/EBP␣) and subsequently increase the expression of the cell cycle inhibitor p21 WAF1/CIP1 (Roth et al, 2002), whereas growth factor-induced increases in cyclin D1 expression and phosphorylation of retinoblastoma protein are reduced (Fernandes et al, 1999).…”

Section: Introductionsupporting

confidence: 68%

“…ASM proliferation is inhibited by glucocorticosteroids (Stewart et al, 1995;Fernandes et al, 1999;Roth et al, 2002). In the present study, the glucocorticosteroids dexamethasone, budesonide, and fluticasone all inhibited both PDGF-induced hypocontractility of intact BTSM strips and BTSM cell proliferation, indicating that these glucocorticosteroids also inhibited growth factor-induced ASM phenotype switching.…”

Section: Discussionmentioning

confidence: 56%

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Glucocorticosteroids and β₂-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

Dekkers

Pehlić

Mariani

et al. 2012

J Pharmacol Exp Ther

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Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to increased airway narrowing in asthma. Increased ASM mass may be caused by exposure to mitogens, including platelet-derived growth factor (PDGF) and collagen type I, which induce a proliferative, hypocontractile ASM phenotype. In contrast, prolonged exposure to insulin induces a hypercontractile phenotype. Glucocorticosteroids and ␤ 2 -adrenoceptor agonists synergize to increase glucocorticosteroid receptor translocation in ASM cells; however, the impact of this synergism on phenotype modulation is unknown. Using bovine tracheal smooth muscle, we investigated the effects of the glucocorticosteroids fluticasone (10 nM), budesonide (30 nM), and dexamethasone (0.1-1 M) and the combination of low concentrations of fluticasone (3-100 pM) and fenoterol (10 nM) on ASM phenotype switching in response to PDGF (10 ng/ml), collagen type I (50 g/ml), and insulin (1 M). All glucocorticosteroids inhibited PDGF-and collagen I-induced proliferation and hypocontractility, with the effects of collagen I being less susceptible to glucocorticosteroid action. At 100-fold lower concentrations, fluticasone (100 pM) synergized with fenoterol to prevent PDGF-and collagen I-induced phenotype switching. This inhibition of ASM phenotype switching was associated with a normalization of the PDGF-induced decrease in the cell cycle inhibitors p21 WAF1/CIP1 and p57 KIP2 . At this concentration, fluticasone also prevented the insulininduced hypercontractile phenotype. At even lower concentrations, fluticasone (3 pM) synergized with fenoterol to inhibit this phenotype switch. Collectively, these findings indicate that glucocorticosteroids and ␤ 2 -agonists synergistically inhibit ASM phenotype switching, which may contribute to the increased effectiveness of combined treatment with glucocorticosteroids and ␤ 2 -agonists in asthma.

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Section: Introductionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 56%

Glucocorticosteroids and β₂-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

Dekkers

Pehlić

Mariani

et al. 2012

J Pharmacol Exp Ther

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“…Such findings have been confirmed in various cohorts of patients [4,[116][117][118] including in severe asthmatics [81]. Whereas, the proliferation of nonasthmatic BSM cells is decreased by steroids [119], that of asthmatic BSM cells is insensitive to steroids [4]. Indeed, glucocorticoids downregulate the proliferation of nonasthmatic BSM cells by decreasing the expression of cyclin D1 and the phosphorylation of retinoblastoma protein, but have no effect on ERK signalling [120].…”

Section: Bsm Hyperplasiasupporting

confidence: 50%

Pathophysiology of bronchial smooth muscle remodelling in asthma

Bara¹,

Ozier²,

Lara³

et al. 2010

European Respiratory Journal

149

136

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Whereas the role of bronchial smooth muscle remains controversial in healthy subjects its role is well established in asthmatics. Bronchial smooth muscle contraction induces airway narrowing. The smooth muscle also contributes to bronchial inflammation by secreting a range of inflammatory mediators, recruiting and activating inflammatory cells, such as mast cells or T-lymphocytes. In addition, bronchial smooth muscle mass is significantly increased in asthma. Such an increase has been related to a deposition of extracellular matrix proteins, and an increase in both cell size and number. However, the mechanisms of this smooth muscle remodelling are complex and not completely understood. The article will review recent data regarding the pathophysiology of bronchial smooth muscle remodelling in asthma.

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“…Corticosteroids can inhibit the induced release of RANTES, IL-8, GM-CSF and MCP-1 from airway smooth muscle cells in vitro, although they are not effective in inhibiting eotaxin release. In addition, they inhibit thrombin-induced airway smooth muscle proliferation through an inhibition of cyclin protein expression [84,85].…”

Section: Resultsmentioning

confidence: 99%

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Chung

2000

Eur Respir J

130

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In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro‐inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T‐cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro‐activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.

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The effect of glucocorticoids on proliferation of human cultured airway smooth muscle

Abstract: 1 Airway smooth muscle proliferation is a significant component of the airway wall remodelling that occurs in asthma. In this study, the effects of glucocorticoids on mitogenic responses of human airway smooth muscle have been examined.

Cited by 103 publications

References 45 publications

Glucocorticosteroids and β₂-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

Glucocorticosteroids and β₂-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

Pathophysiology of bronchial smooth muscle remodelling in asthma

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

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The effect of glucocorticoids on proliferation of human cultured airway smooth muscle

Abstract: 1 Airway smooth muscle proliferation is a significant component of the airway wall remodelling that occurs in asthma. In this study, the effects of glucocorticoids on mitogenic responses of human airway smooth muscle have been examined.

Cited by 103 publications

References 45 publications

Glucocorticosteroids and β2-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

Glucocorticosteroids and β2-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

Pathophysiology of bronchial smooth muscle remodelling in asthma

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Contact Info

Product

Resources

About

Glucocorticosteroids and β₂-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

Glucocorticosteroids and β₂-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling