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

Franke, Jana; Abraham, Getu

doi:10.1016/j.ejphar.2014.07.056

Cited by 9 publications

(10 citation statements)

References 73 publications

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“…The β 2 ‐agonists usually used in veterinary clinical practice may also induce tachyphylaxis leading to a refractory response to repeated doses of adrenergic agonists . Thus, combinations of anti‐inflammatory medicines and bronchodilators may optimise the control of disease by reducing the doses of individual drugs and the risk of adverse events .…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Calzetta

Crupi

Roncada

et al. 2019

Equine Veterinary Journal

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Summary Background Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma‐affected horses. Objectives To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. Study design Pairwise meta‐analysis and meta‐regression analysis. Methods Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random‐effect meta‐regression. One‐point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. Results A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax) or pulmonary resistance (RL). Since only the model resulting for RL passed through the origin (Y‐intercept when X = 0: −0.31, 95% CI −0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2O/L/s (95% CI 0.33–0.94), representing the slope of meta‐regression model (high quality of evidence). Main limitations No long‐term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. Conclusions In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

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Section: Discussionmentioning

confidence: 99%

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Calzetta

Crupi

Roncada

et al. 2019

Equine Veterinary Journal

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“…However, this effect might be celldependent as dexamethasone (100 μM) does not prevent the agonistinduced downregulation in equine bronchial fibroblasts. 49 Prednisolone administration (2 mg/kg PO q24h, 7 days) ameliorates the airway obstruction in SEA, but less so than dexamethasone (0.05 mg/kg PO q24h) despite a similar suppression of cortisol production. 41 In contrast, treatment with prednisolone (1 mg/kg 4 days, 0.75 mg/kg 4 days and then 0.5 mg/kg 4 days, PO) improved the clinical score in SEA similarly to dexamethasone (0.1 mg/kg 4 days, 0.075 mg/kg 4 days and 0.05 mg/kg 4 days, IM) in another study.…”

Section: Systemic Use Of Gcmentioning

confidence: 95%

Glucocorticoid treatment in horses with asthma: A narrative review

Mainguy-Seers

Lavoie

2021

Veterinary Internal Medicne

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Despite substantial research efforts to improve the treatment and outcome of horses with asthma, glucocorticoids (GC) remain the cornerstone of drug treatment of this prevalent disease. The high efficacy of GC to relieve airway obstruction explains their extensive use despite potential deleterious effects. However, much is yet to be uncovered concerning GC use in horses with asthma, including the comparative efficacy of the different drugs, the determination of minimal effective doses and the mechanisms underlying their variable modulation of airway inflammation. The objectives of this structured review were to report and compare the plethora of effects of the various GC used in asthmatic horses with a focus on impact on lung function, airway inflammation, and bronchial remodeling. Adverse effects are also briefly described, with an emphasis on those that have been specifically reported in horses with asthma. Ultimately, we aimed to highlight gaps in the literature and to identify future research areas.

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“…To examine the effect of the ARβ inhibitor, propranolol, the MEK/ERK inhibitor, PD98059, p38 inhibitor, SB203580 or STAT3 inhibitor, S31-201 on NE-induced IL-6 production, cells were pretreated with 1 μM propranolol, 50 μM PD98059, 10 μM SB203580 or 100 μM S31-201 or DMSO (vehicle control) for 30 minutes, and then stimulated with NE (10 μM) and/or sIL-6 receptor (IL-6R: 100 ng/ml). The concentration of NE (0-10 μM), propranolol (1 μM), PD98059 (50 μM), SB203580 (10 μM) and S31-201 (100 μM) was referred from previously reported manuscripts 31 47 48 49 50 . To inhibit the expression of p38, fibroblasts were transfected with 100 nM p38 siRNA (Cell Signaling Technology, Danvers, MA).…”

Section: Methodsmentioning

confidence: 99%

Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis

Uehara

Motegi

Yamada

et al. 2016

Sci Rep

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Raynaud’s phenomenon is frequently observed in systemic sclerosis (SSc) patients, and cold- or stress-induced norepinephrine (NE) has been speculated to be associated with vasoconstriction. Objective was to elucidate the role of NE in fibrosis in SSc. IL-6 is a potent stimulator of collagen production in fibroblasts. NE enhanced IL-6 production and proliferation more significantly in SSc fibroblasts than in normal fibroblasts. Furthermore, the production of IL-6 and phosphorylation of p38 in SSc fibroblasts was enhanced by adrenergic receptor (AR)β agonist, isoproterenol, but not ARα agonist, oxymetazoline. ARβ blocker, propranolol, inhibited NE-induced IL-6 production and phosphorylation of p38 in SSc fibroblasts. NE-induced IL-6 was significantly inhibited by p38 inhibitor, SB203580, suggesting that NE-induced phosphorylation of p38 via ARβ enhances IL-6 production in SSc fibroblasts. NE-induced phosphorylation of ERK1/2 via ARα inhibited IL-6 production in SSc fibroblasts. Combined treatment with NE and endothelin-1 resulted in an additive increase in IL-6 production in SSc fibroblasts. NE-induced IL-6/IL-6 receptor trans-signaling increased the production of collagen type I in SSc fibroblasts, and both propranolol and SB203580 inhibited NE-induced collagen production. These results suggest that cold exposure and/or emotional stress-induced NE might contribute to the skin fibrosis via potentiation of IL-6 production from fibroblasts in SSc.

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

Cited by 9 publications

References 73 publications

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Glucocorticoid treatment in horses with asthma: A narrative review

Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis

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