Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research-UFZ, 04318 Leipzig, Germany.
Institute of Biochemistry, Leipzig University, 04103 Leipzig, Germany.
Int J Mol Sci. 2020 Dec 9;21(24):9371. doi: 10.3390/ijms21249371.
Insights into the modes of action (MoAs) of xenobiotics are of utmost importance for the definition of adverse outcome pathways (AOPs), which are essential for a mechanism-based risk assessment. A well-established strategy to reveal MoAs of xenobiotics is the use of omics. However, often an even more comprehensive approach is needed, which can be achieved using multi-omics. Since the immune system plays a central role in the defense against foreign substances and pathogens, with the innate immune system building a first barrier, we systematically reviewed multi-omics studies investigating the effects of xenobiotics on macrophages. Surprisingly, only nine publications were identified, combining proteomics with transcriptomics or metabolomics. We summarized pathways and single proteins, transcripts, or metabolites, which were described to be affected upon treatment with xenobiotics in the reviewed studies, thus revealing a broad range of effects. In summary, we show that macrophages are a relevant model system to investigate the toxicological effects induced by xenobiotics. Furthermore, the multi-omics approaches led to a more comprehensive overview compared to only one omics layer with slight advantages for combinations that complement each other directly, e.g., proteome and metabolome.
了解外源化学物的作用模式（MoAs）对于定义不良结局途径（AOPs）至关重要，而 AOPs 是基于机制的风险评估的基础。一种揭示外源化学物 MoAs 的成熟策略是使用组学。然而，通常需要更全面的方法，这可以通过使用多组学来实现。由于免疫系统在抵御外来物质和病原体方面起着核心作用，先天免疫系统构成第一道防线，因此我们系统地综述了研究外源化学物对巨噬细胞影响的多组学研究。令人惊讶的是，仅确定了九篇结合蛋白质组学和转录组学或代谢组学的研究论文。我们总结了在综述研究中被描述为受到外源化学物处理影响的途径和单个蛋白质、转录物或代谢物，从而揭示了广泛的影响。总之，我们表明巨噬细胞是一个相关的模型系统，可以研究外源化学物引起的毒理学效应。此外，与仅使用一层组学相比，多组学方法提供了更全面的概述，对于直接互补的组合，如蛋白质组学和代谢组学，具有一些优势。
