title: Oxidative stress and innate immunity responses in cigarette smoke stimulated nasal epithelial cells.
abstract: 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.
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy. Electronic address: pace@ibim.cnr.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy; Scienze e Biotecnologie Mediche e Sperimentali-Pneumologia Sperimentale e Clinica, Università degli Studi, Palermo, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Di Vincenzo
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gerbino
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy.
authors.forename: Andreina
authors.initials: A
authors.lastname: Bruno
authors.affiliation: Medical Affair, Dompé SPA Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Lanata
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy.
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002233:Carbocysteine / Q000494:pharmacology; D002460:Cell Line; D002469:Cell Separation; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005100:Expectorants / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010590:Phalloidine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis
chemical_list: D000199:Actins; D005100:Expectorants; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D012906:Smoke; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D010590:Phalloidine; D002233:Carbocysteine
keywords: CARB; CSE; Cigarette smoke; LPS; Nasal epithelial cells; ROS; Reactive oxygen species; TLR4; carbocysteine; cigarette smoke extracts; lipolysaccharide; reactive oxygen species; toll like receptor 4