Dompe SPA Milan

Milano, Italy

Dompe SPA Milan

Milano, Italy
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Pace E.,National Research Council Italy | Ferraro M.,National Research Council Italy | Siena L.,National Research Council Italy | Scafidi V.,National Research Council Italy | And 6 more authors.
Toxicology Letters | Year: 2013

Cigarette smoke represents the major risk factor for chronic obstructive pulmonary disease (COPD). Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Carbocysteine, an anti-oxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on TLR4 expression and on the TLR4 activation downstream events are largely unknown. This study was aimed to explore whether carbocysteine, in a human bronchial epithelial cell line (16-HBE), counteracted some pro-inflammatory CSE-mediated effects. In particular, TLR4 expression, LPS binding, p21 (a senescence marker), IL-8 mRNA and release in CSE-stimulated 16-HBE as well as actin reorganization in neutrophils cultured with supernatants from bronchial epithelial cells which were stimulated with CSE and/or carbocysteine were assessed. TLR4 expression, LPS binding, and p21 expression were assessed by flow cytometry, IL-8 mRNA by Real Time PCR and IL-8 release by ELISA. Actin reorganization, a prerequisite for cell migration, was determined using Atto 488 phalloidin in neutrophils by flow cytometry and fluorescence microscopy.CSE increased: (1) TLR4, LPS binding and p21 expression; (2) IL-8 mRNA and IL-8 release due to IL-1 stimulation; (3) neutrophil migration. Carbocysteine in CSE stimulated bronchial epithelial cells, reduced: (1) TLR4, LPS binding and p21; (2) IL-8 mRNA and IL-8 release due to IL-1 stimulation; (3) neutrophil chemotactic migration. In conclusion, the present study provides compelling evidences that carbocysteine may contribute to control the inflammatory and senescence processes present in smokers. © 2013 Elsevier Ireland Ltd.


Pace E.,National Research Council Italy | Ferraro M.,National Research Council Italy | Di Vincenzo S.,National Research Council Italy | Di Vincenzo S.,University of Palermo | And 4 more authors.
Toxicology in Vitro | Year: 2014

Cigarette smoke extracts (CSE) may play a significant role in diseases of the upper airway including chronic rhinosinusitis. Even short term exposure of cigarette smoke has adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking. Cigarette smoke alters toll-like receptor 4 (TLR4) expression and activation in bronchial epithelial cells. Carbocysteine is an anti-oxidant and mucolytic agent. The effects of carbocysteine on CSE induced oxidative stress and on associated innate immune and inflammatory responses in nasal epithelial cells are largely unknown. The present study was aimed to assess in CSE stimulated nasal epithelial cells (RPMI 2650) the effects of carbocysteine (10-4M) on: cell survival, intracellular reactive oxygen species (ROS) production, TLR4 expression, LPS binding and neutrophil chemotaxis (actin reorganization). We found that CSE increased ROS production, TLR4 expression, LPS binding and neutrophil chemotaxis and all these events were counteracted by pre-incubating CSE stimulated RPMI 2650 cells with carbocysteine. In conclusion, the present study provides compelling evidence that carbocysteine may be considered a promising therapeutic strategy in chronic inflammatory nasal diseases. © 2013 Elsevier Ltd.


Pace E.,National Research Council Italy | Ferraro M.,National Research Council Italy | Di Vincenzo S.,National Research Council Italy | Di Vincenzo S.,University of Palermo | And 7 more authors.
Cell Stress and Chaperones | Year: 2013

Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10-4 M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclear-related factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10-8 M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin V-positive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSE-mediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance. © 2013 Cell Stress Society International.


PubMed | National Research Council Italy and Dompe SPA Milan
Type: Journal Article | Journal: Toxicology in vitro : an international journal published in association with BIBRA | Year: 2013

Cigarette smoke extracts (CSE) may play a significant role in diseases of the upper airway including chronic rhinosinusitis. Even short term exposure of cigarette smoke has adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking. Cigarette smoke alters toll-like receptor 4 (TLR4) expression and activation in bronchial epithelial cells. Carbocysteine is an anti-oxidant and mucolytic agent. The effects of carbocysteine on CSE induced oxidative stress and on associated innate immune and inflammatory responses in nasal epithelial cells are largely unknown. The present study was aimed to assess in CSE stimulated nasal epithelial cells (RPMI 2650) the effects of carbocysteine (10(-4)M) on: cell survival, intracellular reactive oxygen species (ROS) production, TLR4 expression, LPS binding and neutrophil chemotaxis (actin reorganization). We found that CSE increased ROS production, TLR4 expression, LPS binding and neutrophil chemotaxis and all these events were counteracted by pre-incubating CSE stimulated RPMI 2650 cells with carbocysteine. In conclusion, the present study provides compelling evidence that carbocysteine may be considered a promising therapeutic strategy in chronic inflammatory nasal diseases.

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