State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Environ Int. 2020 May;138:105624. doi: 10.1016/j.envint.2020.105624. Epub 2020 Mar 5.
Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01-100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway.
低剂量抗生素在海洋环境中普遍存在，可能对非靶标水生生物产生负面影响。本研究采用鲤鱼原代巨噬细胞，研究了几种常见抗生素（头孢噻肟、恩诺沙星、四环素、磺胺甲恶唑及其混合物）暴露后的作用机制，并探讨了与核因子-κB（NF-κB）信号通路相关的免疫调节作用。采用 KEGG 通路分析方法，对所有处理组中发现的 66 个差异表达基因进行分析，结果表明，暴露于 100μg/L 抗生素可影响 NF-κB 信号通路的调控，提示 NF-κB 的激活是四类抗生素共有的反应。此外，四种抗生素均可诱导 nf-κb 和 NF-κB 相关细胞因子的表达，qPCR 验证了这一结果，然而，与 LPS 处理（100μg/L）相比，四种抗生素的诱导作用较小。NF-κB 拮抗剂阻断了抗生素的许多免疫作用，为 NF-κB 通路介导四种抗生素的作用提供了证据。此外，暴露于环境相关的低浓度（0.01-100μg/L）抗生素会引起 NF-κB 介导的免疫反应，包括内源性 ROS 生成、抗氧化酶活性以及细胞因子和凋亡的表达。此外，与单一抗生素暴露相比，抗生素混合物的暴露对大多数测试的免疫学参数产生了更大的影响，这表明环境中多种抗生素存在相加作用。本研究表明，鱼类原代巨噬细胞暴露于低剂量抗生素会激活 NF-κB 通路。
