Carola Endes
University of Fribourg, Switzerland
Title: Can a human 3D in vitro lung model be considered as a predictive tool for inhalation toxicology?
Biography
Biography: Carola Endes
Abstract
A potential alternative to replace animal experimentations in the field of inhalation particle toxicology is offered by an established and optimized 3D in vitro triple cell co-culture model of the human alveolar tissue barrier cultured at the air-liquid interface. However, due to the acute life-span of this model, it is not possible to assess long-term particulate-induced effects. Nonetheless, via gene expression profiling it is perceived that long-term hazards can be elucidated in vitro by determination of early-response genes. The objective of this study therefore, is to determine the potential of the 3D in vitro lung model as a predicative tool for the long-term particle-induced inhalatory effects that occur in vivo by using specific pathway analysis. To achieve this, crystalline quartz (DQ12) will be employed as a model particulate due to its known inflammogenic and fibrotic nature in vivo. Specifically, in vitro cell co-cultures will be exposed to aerosolized DQ12 at deposited doses up to 2.5 μg/cm2 and analyzed over a 72 h post-exposure period. Investigation of specific endpoint markers for a (pro-)inflammatory response (IL-1α/β,IL-6, IL-8), apoptosis (CASP8, FASL) and oxidative stress (CAT, PRDX), as well as (pro-)fibrotic events (MMP8, TGF-β, AP-1) will be performed via quantitative real-time polymer-chain reaction array. The findings from this study will provide essential insight towards the progression and use of alternative, in vitro models for inhalatory hazard assessment.