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.

低剂量的抗生素在海洋环境中无处不在，并且可能对非目标水生生物产生负面影响。使用鲤鱼的初级巨噬细胞，我们研究了暴露于几种常见抗生素后的作用机制。头孢噻肟，恩诺沙星，四环素，磺胺单甲辛及其混合物，并探索了与核因子-κB（NF-κB）信号通路相关的免疫调节作用。使用所有治疗中发现的66个差异表达基因进行了KEGG通路分析，结果表明暴露于100μg/ L的抗生素可能会影响NF-κB信号通路的调节，这表明NF-κB的激活是一种在所有四种抗生素中常见的反应。另外，四种抗生素诱导的nf-κbqPCR证实了与NF-κB相关的细胞因子表达，然而，与相同浓度的LPS处理（100μg/ L）相比，四种抗生素的诱导反应较小。NF-κB的拮抗剂阻断了许多抗生素的免疫作用，提供了NF-κB途径介导所有四种抗生素的作用的证据。此外，暴露于与环境相关的低水平（0.01–100μg/ L）抗生素会诱导NF-κB介导的免疫反应，包括内源性ROS的产生，抗氧化酶的活性以及细胞因子的表达和凋亡。此外，暴露于抗生素混合物比暴露于单一抗生素对大多数测试的免疫学参数影响更大，表明环境中多种抗生素的累加效应。