Hymery Nolwenn, Masson Floriane, Barbier Georges, Coton Emmanuel
Université de Brest, EA3882, Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, SFR ScInBioS, ESIAB, Technopôle de Brest Iroise, 29280 Plouzané, France.
Université de Brest, EA3882, Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, SFR ScInBioS, ESIAB, Technopôle de Brest Iroise, 29280 Plouzané, France.
Toxicol In Vitro. 2014 Aug;28(5):940-7. doi: 10.1016/j.tiv.2014.04.003. Epub 2014 Apr 18.
In this study, in vitro cytotoxicity and immunotoxicity of the mycotoxin cyclopiazonic acid (CPA) was evaluated on human cells. To evaluate cytoxicity, several cellular targets were used (CD34+, monocytes, THP-1 and Caco-2). Monocytes were more sensitive to CPA than the THP-1 monocytic cell line after 48h of incubation in the tested conditions. Half maximal inhibitory concentration (IC50) were determined to be 8.5 × 10(-8) and 1.75 × 10(-7)M for monocytes and THP1, respectively, while IC50>1.25 × 10(-7)M was observed for Caco-2 and CD34+ cells. The CPA effect on macrophage differentiation was also examined at non-cytotoxic concentrations. The monocyte differentiation process was markedly disturbed in the presence of CPA. After 6 days of culture, CD71 expression was downregulated, while CD14 and CD11a expressions did not change. Moreover, activated macrophages showed a raised burst activity and TNF-α secretion. Overall, the results indicated that CPA exhibited toxicity on various human cellular models. Moreover, at non-cytotoxic concentrations, CPA disturbed human monocytes differentiation into macrophages. This work contributes to understanding the immunosuppressive properties of this food-related toxin.
在本研究中,评估了霉菌毒素环匹阿尼酸(CPA)对人细胞的体外细胞毒性和免疫毒性。为评估细胞毒性,使用了几种细胞靶点(CD34+、单核细胞、THP-1和Caco-2)。在测试条件下孵育48小时后,单核细胞对CPA的敏感性高于THP-1单核细胞系。单核细胞和THP1的半数最大抑制浓度(IC50)分别确定为8.5×10(-8)和1.75×10(-7)M,而Caco-2和CD34+细胞的IC50>1.25×10(-7)M。还在非细胞毒性浓度下检测了CPA对巨噬细胞分化的影响。在CPA存在下,单核细胞分化过程明显受到干扰。培养6天后,CD71表达下调,而CD14和CD11a表达未改变。此外,活化的巨噬细胞显示出增强的爆发活性和TNF-α分泌。总体而言,结果表明CPA对多种人类细胞模型具有毒性。此外,在非细胞毒性浓度下,CPA干扰了人单核细胞向巨噬细胞的分化。这项工作有助于理解这种与食物相关毒素的免疫抑制特性。