Speaker
Description
Introduction
With the escalating challenges of environmental pollution and climate change, research on chronic non-communicable diseases arising from exposure to various pollutants such as inorganic particles and micro-/nanoplastics has gained significant momentum. Among these, respiratory exposure to particulate matter, a major component of air pollution, has been strongly implicated in the pathogenesis of chronic respiratory diseases. Microplastics, another ubiquitous pollutant, have been detected in both indoor and outdoor environments¹ and even within human lung tissues², raising concerns about their potential health impacts. This increasing plastic burden heightens human exposure through inhalation, ingestion, and dermal contact. Moreover, microplastics can further degrade into nanoscale fragments, which have an even greater capacity to penetrate biological barriers, exacerbating their potential health risks. Among these biological barriers, the airway epithelial barrier serves as the first line of defense against airborne pollutants. However, exposure to microplastics compromises the integrity and functionality of this barrier (Fig. 1), thereby increasing susceptibility to respiratory diseases. Disruption of the airway epithelial barrier is not only linked to chronic respiratory conditions but may also contribute to the development of neurodegenerative diseases through systemic inflammation and neuroimmune interactions.
Figure 1: Transition of inhaled nanoplastics through the alveolar epithelial barrier into the vascular system. (The image has been created using smart.servier.com)
Current in vitro and ex vivo models range from conventional Transwell systems to advanced organ-on-chip platforms3,4, which enable the co-culture of human lung epithelial cells and endothelial cells. Additionally, more sophisticated organotypic lung tissue cultures incorporating both tissue-specific and resident immune cells5 provide valuable insights into the complex interactions between pollutants and the pulmonary microenvironment.
Methods
We designed and fabricated an epithelial barrier-on-a-chip platform5 consisting of easily moldable polydimethylsiloxane layers along with a thin, flexible, and transparent membrane to evaluate exposure to various airborne particles.
Results
The administration of silica and polypropylene nanoparticles to the epithelial barrier-on-chip platform under static and dynamic conditions demonstrated the detrimental effects. Cell viabilities were altered, resulting in increased permeabilities, decreased ZO-1 expressions and increased proinflammatory cytokines.
Discussion
Understanding how exposure to these pollutants disrupts airway epithelial integrity is crucial for elucidating the etiopathogenesis of respiratory and neurodegenerative diseases. Advancing robust preclinical models will not only enhance our mechanistic understanding but also facilitate the development of novel therapeutic strategies to mitigate the health impacts of environmental pollution. The organ-on-chip models are envisaged to serve as robust and reliable substitutes in this context.
Acknowledgement: The funding provided by TUBITAK through 123M406 project is highly appreciated.
References
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Jenner, L.C.; Rotchell, J.M.; Bennett, R.T.; Cowen, M.; Tentzeris, V.; Sadofsky, L.R. Sci. Total Environ. 2022, 831, 15490
Goksel, O., Sipahi, M.I., Yanasik, S., Saglam-Metiner, P., Benzer, S., Sabour-Takanlou, L., Sabour-Takanlou, M., Biray-Avci, C., Yesil-Celiktas, O. Allergy, 2024, 79(11), 2953-2965
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Saglam-Metiner, P., Yildiz-Ozturk, E.; Tetik-Vardarli, A.; Cicek, C.; Goksel, O.; Goksel, T.; Yesil-Celiktas, O. Tissue Cell, 2024, 87, 102319
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