Search results for "roflumilast"

Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro

2012

BACKGROUND AND PURPOSEMucociliary malfunction occurs in chronic obstructive pulmonary disease (COPD) and compromised functions of ciliated bronchial epithelial cells may contribute to this. Cigarette smoke, a major risk factor for COPD, impairs ciliary beat frequency (CBF). cAMP augments CBF. This in vitro study addressed, in differentiated, primary human bronchial epithelial cells, whether roflumilast N-oxide, a PDE4 inhibitor, (i) augments CBF; (ii) prevents the reduction in CBF induced by cigarette smoke extract (CSE); and (iii) protects against the loss of the ciliated phenotype following long-term CSE exposure.EXPERIMENTAL APPROACHAir-liquid interface cultured human bronchial epithelia…

Roflumilast improves corticosteroid resistance COPD bronchial epithelial cells stimulated with toll like receptor 3 agonist

2015

Chronic obstructive pulmonary disease (COPD) is characterised by chronic pulmonary inflammation punctuated by periods of viral exacerbations. Recent evidence suggests that the combination of roflumilast with corticosteroids may improve the compromised anti-inflammatory properties of corticosteroids in COPD. We analyzed differential and combination anti-inflammatory effects of dexamethasone and roflumilast N-oxide in human bronchial epithelial cells (HBECs) stimulated with viral toll like receptor (TLR) agonists. Lung tissue and HBECs were isolated from healthy (n = 15), smokers (n = 12) and smokers with COPD (15). TLR3 expression was measured in lung tissue and in HBECs. IL-8 secretion was …

Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease

2013

Background Glucocorticoid functions are markedly impaired in patients with chronic obstructive pulmonary disease (COPD). The phosphodiesterase 4 inhibitor roflumilast N-oxide (RNO) is the active metabolite of roflumilast approved as a treatment to reduce the risk of exacerbations in patients with severe COPD. Objective We sought to characterize the differential effects of RNO versus corticosteroids and their potential additive/synergistic effect in neutrophils from patients with COPD, thus providing scientific rationale for the combination of roflumilast with corticosteroids in the clinic. Methods Peripheral blood neutrophils were isolated from patients with COPD (n = 32), smokers (n = 7), …

Roflumilast for asthma: Weighing the evidence

2015

Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells

2005

Background: A common pathological feature of chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) is mucus hypersecretion. MUC5AC is the predominant mucin gene expressed in healthy airways and is increased in asthmatic and COPD patients. Recent clinical trials indicate that phosphodiesterase type 4 (PDE4) inhibitors may have therapeutic value for COPD and asthma. However, their direct effects on mucin expression have been scarcely investigated. Methods: MUC5AC mRNA and protein expression were examined in cultured human airway epithelial cells (A549) and in human isolated bronchial tissue stimulated with epidermal growth factor (EGF; 25 ng/ml).…

Perfil farmacológico del roflumilast

2010

Roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-n-(3,5-dichloropyrid-4-yl)benzamide) was the first agent of a novel pharmacological class, selective phosphodiesterase 4 (PDE(4)) inhibitors, approved for the use of chronic obstructive pulmonary disease (COPD). The molecular mechanism of action of roflumilast is inhibition of the PDE(4) isoenzyme with a consequent increase of cyclic adenosine monophosphate. Roflumilast evidently has several pharmacological effects: antiinflammatory, anti-emphysema, and antibiotic actions. This drug also inhibits pulmonary hypertension and reduces mucus hypersecretion. The pharmacological actions leading to these effects are: a) inhibition of reactive oxyg…

Simvastatin Increases the Ability of Roflumilast N-oxide to Inhibit Cigarette Smoke-Induced Epithelial to Mesenchymal Transition in Well-differentiat…

2014

Cigarette smoking contributes to epithelial-mesenchymal transition (EMT) in COPD small bronchi as part of the lung remodeling process. We recently observed that roflumilast N-oxide (RNO), the active metabolite of the PDE4 inhibitor roflumilast, prevents cigarette smoke-induced EMT in differentiated human bronchial epithelial cells. Further, statins were shown to protect renal and alveolar epithelial cells from EMT. To analyze how RNO and simvastatin (SIM) interact on CSE-induced EMT in well-differentiated human bronchial epithelial cells (WD-HBEC) from small bronchi in vitro. Methods: WD-HBEC were stimulated with CSE (2.5%). The mesenchymal markers vimentin, collagen type I and α-SMA, the e…

Estudio del perfil farmacológico de inhibidores de PDE4 en modelos de fibrosis cutánea

2021

La fibrosis es un mecanismo fisiológico que se define como el aumento de la proliferación de fibroblastos y deposición de matriz extracelular (MEC), que, cuando adquiere un carácter patológico, puede destruir la arquitectura normal y producir la disfunción del órgano. La fibrosis cutánea ocurre en una variedad de enfermedades tales como la esclerosis sistémica (ES) o esclerodermia, queloides, cicatrices hipertróficas y otras afecciones. Se considera que es el resultado de una reparación anormal en respuesta al daño tisular. Roflumilast, un inhibidor de la fosfodiesterasa (PDE) 4 aprobado para el tratamiento de la enfermedad pulmonar obstructiva crónica (EPOC), ha demostrado tener efectos an…

Roflumilast N-Oxide Partially Prevents The Loss Of Ciliated Human Airway Epithelial Cells Secondary To Incubation With Cigarette Smoke Extracts In Vi…

2010

PDE4 inhibitors as new anti-inflammatory drugs: effects on cell trafficking and cell adhesion molecules expression.

2004

Phosphodiesterase 4 (PDE4) is a major cyclic AMP-hydrolyzing enzyme in inflammatory and immunomodulatory cells. The wide range of inflammatory mechanisms under control by PDE4 points to this isoenzyme as an attractive target for new anti-inflammatory drugs. Selective inhibitors of PDE4 have demonstrated a broad spectrum of anti-inflammatory activities including the inhibition of cellular trafficking and microvascular leakage, cytokine and chemokine release from inflammatory cells, reactive oxygen species production, and cell adhesion molecule expression in a variety of in vitro and in vivo experimental models. The initially detected side effects, mainly nausea and emesis, appear at least pa…