Direct cigarette smoke exposure to 3D epithelial cell cultures by an aerosol exposure system - Development and evaluation of an in vitro model for COPD with direct cigarette smoke exposure on small airway epithelial cells in the air-liquid interface by the Vitrocell smoking system
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Examensarbete för masterexamen
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Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory and
progressive lung disease that causes obstructed airflow from the lungs. The Global
Burden of Disease Study reports a prevalence of 251 million cases of COPD
globally in 2016 and classify the disease as the third most common causes of
deaths worldwide. Cigarette smoke exposure is one of the major risk factors for
developing COPD. Up to 40% of smokers develop COPD over time, and
continuous smoking drives the development and progression of the disease.
The aim of this project was to develop and evaluate an in vitro model for direct
whole cigarette smoke exposure on small airway epithelial cells (SAECs) with an
automated aerosol system (Vitrocell smoking system). SAECs from three COPD
donors and two healthy donor, cultured in the air-liquid interface (ALI), were used.
To examine the effects of cigarette smoke on airway epithelium, cells were exposed
to either one or three non-toxic doses of smoke, and samples were collected 24 and
48 hours post exposure. Cytotoxicity, barrier integrity, ciliary beat frequency, gene
expression and cytokine expression were investigated. Cigarette smoke effectively
increased the amount of inflammatory mediators IL-6 and IL-8 in supernatants
from smoke-exposed samples, and up-regulated inflammatory gene expression of
IL-8, and gene expression of antioxidants SRXN1 and HMOX1.
This project was performed at AstraZeneca in the Bioscience COPD IPF
Department within the Early Respiratory and Immunology R&D unit located in
Gothenburg, Sweden.
Beskrivning
Ämne/nyckelord
COPD, Small airway epithelial cells, cigarette smoke, Vitrocell system, RT-PCR, air liquid interface, ciliary beat frequency