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Early biomarkers indicating COPD can be induced by whole cigarette smoke in fresh human lung tissue

: Obernolte, Helena; Ritter, Detlef; Knebel, Jan; Braubach, Peter; Jonigk, Danny; Warnecke, Gregor; Zardo, Patrick; Fieguth, Hans-Gerd; Pfennig, Olaf; Braun, Armin; Sewald, Katherina


Pneumologie 72 (2018), Nr.3, S.224
ISSN: 0934-8387
Fraunhofer ITEM ()

Cigarette smoke (Cs) inhalation is one of the main reasons to develop chronic obstructive pulmonary disease (COPD), characterised by degradation of alveoli, emphysema development, inflammation and mucus hypersecretion. Mechanisms that underlie various components of COPD can be modelled in vitro, specifically using whole fresh cigarette smoke. We assessed the effects of Cs and Cs condensate (Csc) on fresh human lung tissue. Human Precision-Cut Lung Slices (PCLS) were exposed to Csc or whole Cs in an Air-Liquid Interface (ALI) using the in vitro exposure device P.R.I.T.® ExpoCube®. Tissue viability, release of cytokines and extracellular matrix (ECM) proteins were analysed after single and repeated exposure and cultivation of up to 96h. Inhibitors were applied to suppress inflammatory responses of tissue to Cs. Csc and Cs induced concentration-dependent loss of tissue viability in fresh lung tissue. Smoke exposure induced an increased release of pro-inflammatory cytokines IL-1α (˜two fold), IL-1β (˜ three fold) and changes in ECM proteins, e.g. MMP-9 and pro-Collagen1α1 (˜ two fold), as well as Receptor for Advanced Glycation Endproducts (RAGE) from human PCLS. Dexamethasone and Roflumilast inhibited Cs-induced increase of pro-inflammatory cytokines. Csc and Cs induced tissue injury, early biomarkers of inflammation and changes in ECM proteins in vital ex vivo human lung tissue. The exposure of the complex mixture of whole cigarette smoke closely reflects the in vivo situation in human lung tissue. Next we will assess the response of human PCLS exposed to Cs and infected with rhinovirus to study exacerbations.