References of "Pulmonary Pharmacology & Therapeutics"
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See detailMatrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?
Garbacki, Nancy ULg; Di Valentin, Emmanuel ULg; Piette, Jacques ULg et al

in Pulmonary Pharmacology & Therapeutics (2009), 22(4), 267-278

Among the large matrix metalloproteinases (MMPs) family, MMP-12, also referred to as macrophage elastase, plays a significant role in chronic pulmonary pathologies characterized by an intense tissue ... [more ▼]

Among the large matrix metalloproteinases (MMPs) family, MMP-12, also referred to as macrophage elastase, plays a significant role in chronic pulmonary pathologies characterized by an intense tissue remodeling such as asthma and COPD. This review will summarize knowledge about MMP-12 structure, functions and mechanisms of activation and regulation, including potential MMP-12 modulation by microRNA. As MMP-12 is involved in many tissue remodeling diseases, efforts have been made to develop specific synthetic inhibitors. However, at this time, very few chemical inhibitors have proved to be efficient and specific to a particular MMP. The relevance of silencing MMP-12 by RNA interference is highlighted. The specificity of this approach using siRNA or shRNA and the strategies to deliver these molecules in the lung are discussed. [less ▲]

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See detailEvaluation of oral corticosteroids and phosphodiesterase-4 inhibitor on the acute inflammation induced by inhaled lipopolysaccharide in human.
Michel, Olivier; Dentener, Mieke; Cataldo, Didier ULg et al

in Pulmonary Pharmacology & Therapeutics (2007), 20(6), 676-83

Background Endotoxins are pro-inflammatory substances present in the environment. In man, inhalation of its purified derivative lipopolysaccharide (LPS) induces inflammation related to macrophages and ... [more ▼]

Background Endotoxins are pro-inflammatory substances present in the environment. In man, inhalation of its purified derivative lipopolysaccharide (LPS) induces inflammation related to macrophages and neutrophils. Corticosteroids and phosphodiesterase (PDE)-4 inhibitors have inhibiting effects on macrophages and neutrophils, respectively. This study investigated the effect of prednisolone and of the PDE-4 inhibitor cilomilast on the LPS-induced acute inflammation. Methods The study was a placebo-controlled, double-blind crossover design. On three occasions, at 2 weeks interval, 16 healthy subjects inhaled 50 μg LPS after a 6-day treatment with cilomilast (15 mg bd), prednisolone (10 mg bd) or placebo. For the assessment of the inflammatory response, induced sputum was obtained before inclusion and 6 h post-LPS while blood samples were collected before, 6 and 24 h post-LPS. Results Inhaled LPS induced an increase in sputum neutrophils (p<0.0001), logMMP-9 (p<0.05), logMMP-9/TIMP-1 (p<0.01) and logTNF-α (p<0.02). At the blood level there were significant rise in neutrophilia (p<0.001), E-selectin (p<0.02), C-reactive protein (CRP) (p<0.001) and LPS-binding protein (p<0.001). There was both a slight, but not significant, increase in body temperature and decrease in forced expiratory volume in 1 s (FEV1). Neither prednisolone nor cilomilast had protective effect on the LPS-induced airways’ inflammation. The LPS-induced CRP acute-phase protein of inflammation (0.58±0.13 and 3.52±0.41 mg/dL, before and after LPS, respectively) was significantly inhibited by a pre-treatment with prednisolone (1.39±0.32 mg/dL, p<0.01) and attenuated (2.65±0.30 mg/dL, p=0.09) with cilomilast. Conclusion In healthy subjects, while the LPS-induced airways’ inflammation was not modified either by oral prednisolone or by PDE-4 inhibitor cilomilast (at actual dosage), the LPS-induced acute phase of blood inflammation was reduced by prednisolone. [less ▲]

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See detailThe triple neurokinin-receptor antagonist CS-003 inhibits neurokinin A-induced bronchoconstriction in patients with asthma
Schelfhout, V.; Louis, Renaud ULg; Lenz, W. et al

in Pulmonary Pharmacology & therapeutics (2006), 19(6), 413-418

Neurokinin A (NKA) causes bronchoconstriction in asthmatic patients. In vitro both NK1 and NK2 receptors can mediate airway contraction. Moreover in guinea pigs, NK3 receptors facilitate cholinergic ... [more ▼]

Neurokinin A (NKA) causes bronchoconstriction in asthmatic patients. In vitro both NK1 and NK2 receptors can mediate airway contraction. Moreover in guinea pigs, NK3 receptors facilitate cholinergic neurotransmission. Dual tachykinin NK1/NK2 receptor antagonism results in prevention of NKA-induced bronchoconstriction. We have now examined the effect of a single dose of the triple tachykinin receptor antagonist CS-003 on NKA-induced bronchoconstriction in asthmatics. A double blind, crossover, placebo-controlled trial in 16 mild asthmatics was performed. One single dose of CS-003 (200 mg, solution in distilled water) or matched placebo was given orally on the assessment days. NKA-provocation tests were performed pre-dose and 1, 8 and 24h after dosing. There was a significant shift to the right of the dose-response curve at 1 and 8 h after intake of CS-003. PC20 was not reached in 12/16 patients at 1 h post-dose and in 5/16 patients at 8h post-dose. This did not occur under placebo treatment. A single dose of 200 mg CS-003 protected significantly against NKA-induced bronchoconstriction at 1 and 8 h post-dose in mild asthmatics. (c) 2005 Elsevier Ltd. All rights reserved. [less ▲]

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See detailVariations in systemic and pulmonary endothelin-1 in horses with recurrent airway obstruction (heaves)
Benamou, A. E.; Art, Tatiana ULg; Marlin, D. J. et al

in Pulmonary Pharmacology & Therapeutics (1998), 11

Recurrent airway obstruction (RAO) is an asthma-like condition of the horse that represents a major cause of morbidity and loss of performance. The exact pathogenesis of asthma in man is unclear but the ... [more ▼]

Recurrent airway obstruction (RAO) is an asthma-like condition of the horse that represents a major cause of morbidity and loss of performance. The exact pathogenesis of asthma in man is unclear but the role of endothelin (ET) is currently under investigation, thus sparking interest in the bronchoconstrictive and vasoconstrictive properties of endothelin in the equine-specific disease entity. In this study, we investigated the levels of ET-1 in systemic blood, as well as in bronchoalveolar lavage (BAL) from horses with RAO. We also studied how these values might correlate with those of lung function tests and pulmonary artery pressure. Five horses with RAO were evaluated both in remission and in crisis and compared to five control horses. RAO horses had significantly (P<0.05) higher systemic ET-1 levels than control horses. They also had a negative arteriovenous ET-1 difference that may correspond to a net uptake of ET-1 in the lung. RAO horses in crisis had increased amounts of immunoreactive ET in BAL fluid compared to normal control subjects. Additionally, the reduction in lung function seen in RAO horses in crisis was significantly correlated with lower epithelial lining fluid ET-1 levels. Our results demonstrate that endothelin may contribute to the pathogenesis of asthma. [less ▲]

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