Aspergillus fumigatus toxins cause cytotoxic and apoptotic effects on human T lymphocytes (Jurkat cells)

作者：Malekinejad H^*; Fani M; Hassani Dizaji S; Shafie Irannejad V; Fink Gremmels J

来源：World Mycotoxin Journal, 2013, 6(1): 65-71.

DOI：10.3920/WMJ2012.1481

• Aspergillus fumigatus
• cytotoxicity
• fumagillin
• gliotoxin
• kojic acid
• verruculogen

Aspergillus fumigatus is a ubiquitous fungus, which plays a prominent role in the incidence of various diseases including invasive aspergillosis. The cytotoxicity and apoptotic effects of the main secondary metabolites of Aspergillus fumigatus including gliotoxin, kojic acid, fumagillin, and verruculogen were studied on human T lymphocytes (Jurkat cells). The calculated IC50 values, which were obtained based on the Alamar Blue reduction assay, indicated that the strongest toxicity was exerted by gliotoxin, followed by kojic acid and equally by fumagillin and verruculogen. Correspondingly, the evaluation of reactive oxygen species (ROS) production by the selected mycotoxins showed that gliotoxin exposure resulted in the highest ROS generation, followed by kojic acid, fumagillin and verruculogen. Each of the four mycotoxins exhibited concentration- and time-dependent apoptotic effects albeit with differences as evidenced by cytochrome C release, caspase-3/7 activity enhancement, and DNA fragmentation. In conclusion, a comparison of gliotoxin and other metabolites of A. fumigatus such as kojic acid, fumagillin and verruculogen identified gliotoxin as the most cytotoxic mycotoxin for Jurkat cells. As Jurkat cells represent human T lymphocytes, A. fumigatus toxins might exert significant immunosuppressive effects.

• 出版日期2013-2