1,720,983 research outputs found
P38 signalling pathway in primary cultures of human bronchial epithelial cells: effects of transforming growth factor-β and pharmacological modulation by budesonide
No full textBronchial epithelial cells play a central role in airway remodelling associated with asthma. In this process, a key function is exerted by transforming growth factor-β (TGF-β), whose biological effects are mediated at least in part by mitogen-activated protein kinases (MAPK). Therefore, the main aim of our study was to investigate, in primary cultures of human bronchial epithelial cells (HBEC), the effects of TGF-β on MAPKp38 phosphorylation. In addition, since we have previously shown in human pulmonary endothelial cells that dexamethasone is able to inhibit MAPK activation, a further objective of our research was to verify whether glucocorticoids might interfere with MAPK signalling also in HBEC.
After being obtained from fresh surgical specimens, HBEC were grown to confluence and incubated for 2 h with TGF-β1 (10 ng/ml), in the presence or in the absence of a pretreatment with budesonide (10-8 M, for 12 h). Activated p38 was detected by Western blotting, using an anti-phospho-p38 monoclonal antibody that specifically recognizes the phosphorylated, active forms of this MAPK subgroup. TGF-β induced a 5-fold increase in p38 phosphorylation, which was fully prevented by budesonide.
Our results provide valuable information about the signal transduction pathways mediating the biological effects of TGF-β in airway epithelium, which represents the first and one of the most important targets of inhaled glucocorticoids such as budesonide. Therefore, the powerful inhibitory effect on p38 phosphorylation-dependent activation, exerted by this drug in bronchial epithelial cells, may significantly contribute to its therapeutic action in asthma
Comparative evaluation of the protective effect of broxaterol and salbutamol in bronchial spasm induced with an ultrasonic aerosol of distilled water
No full text
Effects of specific immunotheraphy in allergic rhinitic individuals with bronchial hyperresponsiveness
No full text
Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease.
No full textUpdate on optimal use of omalizumab in management of asthma
No full textGirolamo Pelaia1, Luca Gallelli1, Teresa Renda1, Pasquale Romeo1, Maria Teresa Busceti1, Rosa Daniela Grembiale1, Rosario Maselli1, Serafino Antonio Marsico2, Alessandro Vatrella31Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Catanzaro; 2Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples; 3Department of Respiratory Medicine, University of Salerno, Salerno, ItalyAbstract: Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing interaction with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include improvements in respiratory symptoms and quality of life, paralleled by a reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well-tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma inadequately controlled by high doses of standard inhaled treatments.Keywords: omalizumab, anti-IgE, severe asthm
Effects of transforming growth factor-[beta] and budesonide on mitogen-activated protein kinase activation and apoptosis in airway epithelial cells.
No full textAirway epithelial cells play a central role in the inflammatory, apoptotic, and remodeling processes associated with asthma. Within this context, a key function is exerted by transforming growth factor-beta (TGF-beta), whose biological effects are mediated at least in part by mitogen-activated protein kinases (MAPKs). The aim of our study was to investigate, in primary cultures of human bronchial epithelial cells (HBEC), the effects of TGF-beta (10 ng/ml) on both MAPK activation and apoptosis, in the presence or absence of a pretreatment with budesonide (10-8 M). MAPK activation was detected by Western blotting, using anti-phospho-MAPK monoclonal antibodies, which specifically recognize the phosphorylated, active forms of these enzymes. Apoptosis was assayed by caspase-3 activation and fluorescence microscopy, using annexin-V (An-V) and propidium iodide (PI) as markers of cell death. Our results show that TGF-beta induced a marked ( reverse similar 9-fold) increase in p38 MAPK phosphorylation, and also dramatically enhanced cell death, which was completely prevented by specific MAPK inhibitors. Both MAPK activation and apoptosis were effectively inhibited by budesonide (BUD), thereby suggesting that the powerful antiapoptotic action of inhaled glucocorticoids may be very important for their protective role against epithelial injury, which represents a key pathogenic event in asthma
Comparison of the bronchodilating effects of inhaled formoterol, salmeterol and salbutamol in asthmatic patients.
No full textTen subjects with various degrees of asthma severity underwent a three-day trial, with the aim of
evaluating the bronchodilating effect of inhaled formoterol (12 mg), in comparison with salbutamol (200 mg) and
salmeterol (50 mg). The bronchodilation afforded by formoterol paralleled that of salbutamol in rapidity (mean
percentage increases in functional measurements (FEV1) vs. baseline recorded 5 min after drug administration:
7.7%, 9.3%, and 0.3% for salbutamol, formoterol and salmeterol, respectively) and that of salmeterol in duration
(mean percentage increases in FEV1 vs. baseline recorded 12 h after drug administration: 16.8% and 15.9% for
formoterol and salmeterol, respectively). Moreover, the maximal effect of formoterol resulted to be slightly higher
in comparison with salbutamol (P50.001) and salmeterol (P50.05); in this regard, the mean percentage increases
in FEV1 vs. baseline recorded 2 h after salbutamol and formoterol, and 4 h after salmeterol were 22.3%, 29.5%, and
24.6%, respectively. Therefore, these results suggest that formoterol can be used, in addition to its utilization as
long-acting bronchodilator, also as an effective rescue medication for the immediate relief of asthma symptoms
- …
