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Cigarette smoke condensate and cigarette smoke induce cytotoxicity and inflammation in human and rodent Precision-Cut Lung Slices of different species

 
: Obernolte, Helena; Konzok, Sebastian; Ritter, Detlef; Knebel, Jan W.; Braubach, Peter; Jonigk, Danny; Braun, Armin; Sewald, Katherina

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Pneumologie 69 (2015), No.7, pp.69 - A17
ISSN: 0934-8387
International Symposium "Frontiers in Chronic and Malignant Airways Disease" <4, 2015, Heidelberg>
English
Abstract
Fraunhofer ITEM ()

Abstract
Chronic obstructive pulmonary disease (COPD) is a common irreversible severe lung disease. It is characterized by airway inflammation and progressive destruction of lung tissue resulting in emphysema. COPD is therefore a main cause for mortality and morbidity worldwide. A major reason to develop COPD is cigarette smoking. Lipopolysaccharides are commonly used pro-inflammatory model compounds but can not entirely reflect cigarette smoke features of COPD. The aim of the study is to establish a model of COPD in Precision-Cut Lung Slices (PCLS) of different species, including human, using cigarette smoke (Cs) and cigarette smoke condensate (Csc).Human and rodent PCLS were prepared and exposed to Cs at Air-Liquid Interface or submerse to Csc and LPS. Induced toxicity was assessed by WST-1 assay, LIVE/DEAD vitality staining and measurement of lactate dihydrogenase (LDH) in slices exposed to Cs and Csc. Pro-inflammatory immune responses were determined by measurement of cytokines by ELISA. Therapeutical intervention was assessed by using dexamethasone. Concentration dependent toxicity after exposure to Csc was assessed with EC50 values of 85 µg/mL in murine PCLS, 212 µg/mL in rat PCLS and 196 µg/mL in human PCLS. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α) showed increased release from murine and human PCLS after Csc exposure. Release was inhibited by therapeutical intervention using dexamethasone in human PCLS.Cs induced tissue injury in rat PCLS. Csc induced toxicity in human and rodent PCLS. PCLS represent a promising model to receive translational data about toxic and inflammatory aspects of Cs and Csc indifferent species.

: http://publica.fraunhofer.de/documents/N-397716.html