Atalay Begüm Rana, Başkan Ömer Mete, Ercan Semanur, Aydın Ece, Ayaz Furkan, Aydemir Esra
Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, 34010, Türkiye.
Department of Pharmacy, Faculty of Pharmacy, Biruni University, Istanbul, 34010, Türkiye.
Immunol Res. 2025 Apr 21;73(1):73. doi: 10.1007/s12026-025-09631-8.
A plethora of the cancer drugs with high therapeutic potential cannot pass the clinical trials because of their immunotoxic activities. In this study, we tested the immunomodulatory and immunostimulatory effects of the anticancer agent alexidine dihydrochloride on J774.2 macrophage cell lines in vitro. The production levels of the pro-inflammatory cytokines (TNF-α, IL-6, GM-CSF, IL-12p40) were measured and compared by ELISA method. The activated (phosphorylated) JNK protein levels were measured by flow cytometer and the possible related intracellular signaling pathway was examined in this way. According to our results, alexidine dihydrochloride has an anti-inflammatory effect on the LPS-stimulated macrophage cell lines, as evidenced by reduced cytokine production compared to controls. Furthermore, its intracellular mechanism of action was found to be mediated partially through JNK signaling pathways. These findings suggest that alexidine dihydrochloride, while being an effective anticancer agent, may also modulate immune responses by dampening excessive inflammation. In this study, determining the anti-inflammatory effect of alexidine dihydrochloride on the immune system will seriously shed light on the role of this anticancer agent in future clinical studies and will provide a serious basis. In summary, the effects of the most drug-active ingredients on the inflammatory response in immune system cells have not been fully tested, and this creates the problem of many drugs failing in clinical studies or lack of knowledge on their side effects. Our study aimed to determine the effect of alexidine dihydrochloride, used as an anticancer agent, on the inflammatory response in J774.2 macrophage cell lines. Future studies with more immune system cells and a wider analysis of the intracellular signaling pathways will be informative about the immunotoxicity of the drug molecule. Future research involving a broader range of immune cell types and a more comprehensive analysis of intracellular signaling pathways will help clarify the immunotoxicity profile of this anticancer agent.
大量具有高治疗潜力的抗癌药物由于其免疫毒性活性而无法通过临床试验。在本研究中，我们在体外测试了抗癌剂盐酸阿来西定对J774.2巨噬细胞系的免疫调节和免疫刺激作用。通过ELISA方法测量并比较促炎细胞因子（TNF-α、IL-6、GM-CSF、IL-12p40）的产生水平。通过流式细胞仪测量活化（磷酸化）的JNK蛋白水平，并以此方式检查可能相关的细胞内信号通路。根据我们的结果，盐酸阿来西定对LPS刺激的巨噬细胞系具有抗炎作用，与对照组相比，细胞因子产生减少证明了这一点。此外，发现其细胞内作用机制部分通过JNK信号通路介导。这些发现表明，盐酸阿来西定虽然是一种有效的抗癌剂，但也可能通过减轻过度炎症来调节免疫反应。在本研究中，确定盐酸阿来西定对免疫系统的抗炎作用将为该抗癌剂在未来临床研究中的作用提供重要线索，并将提供重要依据。总之，大多数药物活性成分对免疫系统细胞炎症反应的影响尚未得到充分测试，这导致许多药物在临床研究中失败或对其副作用缺乏了解的问题。我们的研究旨在确定用作抗癌剂的盐酸阿来西定对J774.2巨噬细胞系炎症反应的影响。未来对更多免疫系统细胞进行研究并更广泛地分析细胞内信号通路，将有助于了解该药物分子的免疫毒性。涉及更广泛免疫细胞类型范围和对细胞内信号通路进行更全面分析的未来研究，将有助于阐明这种抗癌剂的免疫毒性特征。
