Effect of cilomilast (Ariflo) on TNF-α, IL-8, and GM-CSF release by airway cells of patients with COPD

Background: Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a novel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, exerts anti-inflammatory effects. The ability of cilomilast to inhibit the release of neutrophil chemoattractants such as tumour necrosis factor (TNF)-α, interleukin (IL)-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) by bronchial epithelial cells and sputum cells isolated from 10 patients with COPD, 14 normal controls, and 10 smokers was investigated. Methods: Bronchial epithelial cells obtained by bronchial brushing and sputum…

“Smoke, Choline-Acetyl-Transferase, Muscarinic Receptors and fibroblast proliferation in COPD

Acetylcholine (ACh), synthesized by choline acetyltransferase (ChAT), and muscarinic M1, M2, and M3 receptors (MRs) are involved in fibroblast proliferation. We evaluated ChAT, MRs, and extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor (NF) κB activation in lung fibroblasts from patients with chronic obstructive pulmonary disease (COPD), control smokers, and controls. Human fetal lung fibroblasts (HFL-1) stimulated with interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and cigarette smoke extracts (CSEs) were evaluated for ChAT and MR expression. We tested the effects of ACh on fibroblast proliferation and its ability to bind fibroblasts from patients with COPD, control s…

Urinary leukotriene E4 in the assessment of nocturnal asthma

Urinary leukotriene E4 (LTE4) is a marker of the body's production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest.This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE4, and the relationship between the two phenomena.Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytime FEV1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow greater than 20%). Urine wa…

Role of non cholinergic system components in Chronic rhinosinusitis and nasal polips

15-Lipoxygenase expression and 15(S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects

Recent evidence shows that 15(S)-hydroxy-eicoisatetraenoic acid (15[S]-HETE) can be released and rapidly reincorporated into cellular lipids. These mechanisms exert several immunoregulatory functions that may be relevant in airway inflammation.Our purpose was to evaluate the levels of both soluble and cell-associated 15(S)-HETE and to examine 15-lipoxygenase (15-LO) messenger RNA (mRNA) expression in sputum samples obtained from 10 control and 18 asthmatic subjects.Levels of 15(S)-HETE were measured by reverse-phase HPLC separation followed by RIA in supernatants and in cell membrane-extracted phospholipids after acid hydrolysis. 15-LO mRNA was evaluated by primed in situ hybridization (PRI…

In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics

Corticosteroids play an important role in inflammation and remodelling of airways and are considered an important therapeutic target in asthma. Inflammation in asthma is characterized by a dysregulation of eosinophil apoptosis and of markers of airways remodelling. We evaluated the ability of flunisolide to inhibit in vitro the release of metalloproteinases-9 (MMP-9), tissue inhibitor metalloproteinases-1 (TIMP-1), transforming growth factor (TGF-beta) and fibronectin by sputum cells (SC) as well as to induce sputum eosinophil apoptosis.The SC, isolated from induced sputum samples of 12 mild-to-moderate asthmatics, were cultured for 24 h in the presence or absence of flunisolide (1, 10 and …

Bronchial hyperresponsiveness (BHR) or exhaled nitric oxide concentration (eNO) do not predict exercise-induced bronchoconstriction (EIB) in atopic children with intermittent asthma

Pleural Mesothelial Cells Express Both BLT2 and PPAR and Mount an Integrated Response to Pleural Leukotriene B4

Leukotriene B(4) (LTB(4)) plays a crucial role in the recruitment of neutrophils into the pleural space. We identified for the first time the mechanisms by which LTB(4) interacts with mesothelial cells and recruits neutrophils in the pleural compartment. Primary pleural mesothelial cells express both the proinflammatory receptor for LTB(4) BLT2, and the anti-inflammatory receptor for LTB(4), PPARalpha. Parapneumonic pleural effusions highly increase BLT2 expression and, via BLT2 activation, increase the adhesion between mesothelial cells and neutrophils and the expression of ICAM-1 on mesothelial cells. The block of PPARalpha further increases both cell adhesion and ICAM-1 expression. BLT2 …

OZONE EXPOSURE INCREASES EXERCISE-INDUCED PULMONARY DAMAGE AND INFLAMMATION IN NONASTHMATIC LONG-DISTANCE RUNNERS

IL-13 induced beta2-adrenergic receptor (beta2-AR) desensitization in human airway epithelial cells.

IL-17 and Th17-cells as markers of disease progression in pediatric allergic diseases. A therapeutic approach in an “in vitro” model

Rationale: Th17 cells and IL-17 play a role in allergy development and progression. Objective: To investigate whether IL-17-producing Th17 cells characterized systemic and airway inflammation in children with concomitant allergic rhinitis and asthma and whether Budesonide (Bud) and Formoterol (Form), alone or in combination, might provide a therapeutic strategy for controlling the inflammatory events associated with IL-17. Methods: We tested IL-17 levels in plasma (P), nasal wash (NW) and induced sputum (IS) from healthy (HC) and asthmatic children (intermittent=IA or mild-moderate=MA) with concomitant rhinitis (intermittent=IR or persistent=PR). Then we tested the expression of intracellul…