Area of Toxicology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
Toxins (Basel). 2023 Apr 20;15(4):301. doi: 10.3390/toxins15040301.
Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. However, research on its potential immunotoxicity is still limited. Thus, this study aimed to evaluate the impact of CYN on two human cell lines representative of the immune system: THP-1 (monocytes) and Jurkat (lymphocytes). CYN reduced cell viability, leading to mean effective concentrations (EC50 24 h) of 6.00 ± 1.04 µM and 5.20 ± 1.20 µM for THP-1 and Jurkat cells, respectively, and induced cell death mainly by apoptosis in both experimental models. Moreover, CYN decreased the differentiation of monocytes to macrophages after 48 h of exposure. In addition, an up-regulation of the mRNA expression of different cytokines, such as interleukin (IL) 2, IL-8, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), was also observed mainly after 24 h exposure in both cell lines. However, only an increase in TNF-α in THP-1 supernatants was observed by ELISA. Overall, these results suggest the immunomodulatory activity of CYN in vitro. Therefore, further research is required to evaluate the impact of CYN on the human immune system.
柱孢藻毒素（CYN）是一种出现频率越来越高的蓝藻毒素，因此阐明其毒性特征非常重要。CYN 已被归类为细胞毒素，尽管科学文献已经表明它会影响广泛的器官和系统。然而，关于其潜在免疫毒性的研究仍然有限。因此，本研究旨在评估 CYN 对两种代表免疫系统的人类细胞系：THP-1（单核细胞）和 Jurkat（淋巴细胞）的影响。CYN 降低了细胞活力，导致 THP-1 和 Jurkat 细胞的 24 小时有效浓度（EC50）分别为 6.00 ± 1.04 µM 和 5.20 ± 1.20 µM，并在两种实验模型中主要通过细胞凋亡诱导细胞死亡。此外，CYN 在暴露 48 小时后降低了单核细胞向巨噬细胞的分化。此外，还观察到不同细胞因子（如白细胞介素（IL）2、IL-8、肿瘤坏死因子-α（TNF-α）和干扰素-γ（INF-γ））的 mRNA 表达在上调，主要在暴露 24 小时后在两种细胞系中观察到。然而，只有在 THP-1 上清液中观察到 TNF-α 的增加。总体而言，这些结果表明 CYN 在体外具有免疫调节活性。因此，需要进一步研究评估 CYN 对人类免疫系统的影响。
