Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Institute of Applied Biosciences, 76131 Karlsruhe, Germany.
Karlsruhe Institute of Technology (KIT), Institute of Biological and Chemical Systems, Biological Information Processing, 76344 Eggenstein-Leopoldshafen, Germany.
Int J Mol Sci. 2022 Jun 8;23(12):6412. doi: 10.3390/ijms23126412.
The occupational exposure to particles such as crystalline quartz and its impact on the respiratory tract have been studied extensively in recent years. For hazard assessment, the development of physiologically more relevant in-vitro models, i.e., air-liquid interface (ALI) cell cultures, has greatly progressed. Within this study, pulmonary culture models employing A549 and differentiated THP-1 cells as mono-and co-cultures were investigated. The different cultures were exposed to α-quartz particles (Min-U-Sil5) with doses ranging from 15 to 66 µg/cm under submerged and ALI conditions and cytotoxicity as well as cytokine release were analyzed. No cytotoxicity was observed after ALI exposure. Contrarily, Min-U-Sil5 was cytotoxic at the highest dose in both submerged mono- and co-cultures. A concentration-dependent release of interleukin-8 was shown for both exposure types, which was overall stronger in co-cultures. Our findings showed considerable differences in the toxicological responses between ALI and submerged exposure and between mono- and co-cultures. A substantial influence of the presence or absence of serum in cell culture media was noted as well. Within this study, the submerged culture was revealed to be more sensitive. This shows the importance of considering different culture and exposure models and highlights the relevance of communication between different cell types for toxicological investigations.
近年来,人们对晶体石英等颗粒物质的职业暴露及其对呼吸道的影响进行了广泛研究。为了进行危害评估,生理相关性更强的体外模型(即气液界面(ALI)细胞培养)得到了极大的发展。在本研究中,采用 A549 和分化的 THP-1 细胞作为单核和共培养物的肺培养模型进行了研究。将不同的培养物在浸没和 ALI 条件下用 α-石英颗粒(Min-U-Sil5)进行暴露,剂量范围为 15 至 66 µg/cm,并分析细胞毒性和细胞因子释放。在 ALI 暴露后没有观察到细胞毒性。相反,在浸没的单核和共培养物中,Min-U-Sil5 在最高剂量下均具有细胞毒性。两种暴露类型均显示出白细胞介素-8 的浓度依赖性释放,共培养物中的释放总体更强。我们的研究结果表明,ALI 和浸没暴露以及单核和共培养物之间的毒理学反应存在显著差异。还注意到细胞培养物中存在或不存在血清对细胞毒性的显著影响。在本研究中,发现浸没培养更敏感。这表明考虑不同的培养和暴露模型的重要性,并强调了不同细胞类型之间的交流对于毒理学研究的相关性。