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Cigarette smoke and cigarette smoke condensate exposure induces cytotoxicity and inflammation in precision-cut lung slices

: Obernolte, Helena; Konzok, Sebastian; Ritter, Detlef; Knebel, Jan; Braubach, Peter; Jonigk, Danny; Fieguth, Hans-Gerd; Braun, Armin; Sewald, Katherina


Toxicology letters 238 (2015), Nr.2, Supplement, S.S329-S330
ISSN: 0378-4274
ISSN: 1879-3169
European Societies of Toxicology (EUROTOX Congress) <51, 2015, Porto>
Fraunhofer ITEM ()

Chronic obstructive pulmonary disease (COPD) is characterized by progressive destruction of the lung parenchyma resulting in emphysema and chronic inflammation of the airways. COPD is the fourth leading cause of death and more than 200 million people are affected worldwide. The major risk factor to develop COPD is cigarette smoke. Nowadays, lipopolysaccharide (LPS) is a widely used model compound which induces inflammation but cannot entirely reflect cigarette smoke induced toxicity and cytokine release in the lung. To understand the underlying mechanisms of cigarette smoke induced lung inflammation and destruction the need emerged to develop human relevant models. Aim of the study is to establish features of COPD in precision-cut lung slices (PCLS)of different species, including human, by exposure with cigarette smoke and cigarette smoke condensate (Csc). Murine, rat and human PCLS were prepared and exposed to Csc and LPS submersely or to cigarette smok eat air liquid interface (ALI). Induced toxicity was assessed by detection of lactate dehydrogenase, LIVE/DEAD® vitality staining and measurement of metabolic activity by usingWST-1 assay. Induction of pro-inflammatory immune responses was determined by ELISA. Therapeutical intervention was assessed by using dexamethasone. Concentration dependent toxicity was assessed after exposure to Csc with EC50 values of 85 μg/ml in murine PCLS, 228 μg/ml in rat PCLS and 121 μg/ml in human PCLS by measurement of metabolic activity. Csc exposure induced an increased release of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1α/1β (IL-1α, IL-1β) in murine and human PCLS. For mouse, TNF-α secretion was three fold increased compared to medium control. Csc and cigarette smoke induced tissue damage in murine, rat and human PCLS or in rat PCLS, respectively. Therefore, PCLS from different species represent a promising model to provide translational data about toxic and pro-inflammatory aspects of cigarette smoke. Furthermore, pharmacological intervention against inflammation can be studied in PCLS.