caa a22 4500 606235663 CHVBK 20210128101243.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2476-1 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2476-1 MD2 expression is reduced in large airways of smokers and COPD smokers [Elektronische Daten] [Elisabetta Pace, Maria Ferraro, Giuseppina Chiappara, Patrizio Vitulo, Loredana Pipitone, Serena Di Vincenzo, Mark Gjomarkaj] Toll-like receptor 4 (TLR4) signaling requires a number of accessory proteins to initiate a signal. MD-2 is one of the accessory proteins with a relevant role in lipopolysaccharide responses. Although cigarette smoke increases TLR4 expression, TLR4 signaling is altered in smokers and in smokers COPD patients. The main aims of this study were to explore whether MD2 is altered in large and small airways of COPD and of smokers without COPD. The expression of MD2 ex vivo was assessed by immunohistochemistry in surgical specimens from current smokers COPD (s-COPD; n=14), smokers without COPD (S; n=7), and from non-smoker non-COPD subjects (C; n=11. The in vitro effects of cigarette smoke extracts on the MD2 expression in a human bronchial epithelial cell line (16-HBE) were also assessed by flow cytometry. MD2 is reduced in the epithelium and in the submucosa in large airways but not in the epithelium and in the submucosa in small airways of smokers and of s-COPD. The expression of MD2 in the submucosa of the large airways is significantly higher in comparison to the submucosa of the small airways in all the studied groups. In vitro, cigarette smoke is able to increase TLR4 but it reduces MD2 in a dose-dependent manner in bronchial epithelial cells. Cigarette smoke may alter innate immune responses reducing the expression of the MD2, a molecule with an important role in TLR4 signaling. Springer Science+Business Media New York, 2015 Cigarette smoke nationallicence TLR4/MD2 nationallicence COPD nationallicence Bronchial epithelial cells nationallicence TLR4 : Toll-like receptor 4 nationallicence COPD : Chronic obstructive pulmonary disease nationallicence CSE : Cigarette smoke extracts nationallicence LPS : Lipopolysaccharide nationallicence MD-2 : Myeloid differentiation-2 nationallicence Pace Elisabetta Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut Ferraro Maria Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut Chiappara Giuseppina Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut Vitulo Patrizio Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy aut Pipitone Loredana Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy aut Di Vincenzo Serena Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut Gjomarkaj Mark Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 289-297 0300-8177 407:1-2<289 2015 407 11010 https://doi.org/10.1007/s11010-015-2476-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2476-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pace Elisabetta Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut NATIONALLICENCE 700 1- Ferraro Maria Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut NATIONALLICENCE 700 1- Chiappara Giuseppina Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut NATIONALLICENCE 700 1- Vitulo Patrizio Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy aut NATIONALLICENCE 700 1- Pipitone Loredana Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy aut NATIONALLICENCE 700 1- Di Vincenzo Serena Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut NATIONALLICENCE 700 1- Gjomarkaj Mark Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Via Ugo La Malfa, 153, 90146, Palermo, Italy aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 289-297 0300-8177 407:1-2<289 2015 407 11010