Gliotoxin

Gliotoxin is a secondary metabolite, the most abundant mycotoxin secreted by A. fumigatus, inhibits the phagocytosis of macrophages and the immune functions of other immune cells ^[1]. Gliotoxin inhibits inducible NF-κB activity by preventing IκB degradation, which consequently induces host-cell apoptosis^[2]. Gliotoxin activates PKA and increases intracellular cAMP concentration; modulates actin cytoskeleton rearrangement to facilitate A. fumigatus internalization into lung epithelial cells^[3]. Gliotoxin is a potent NOTCH2 transactivation inhibitor, can effectively induce apoptosis of chronic lymphocytic leukemia (CLL) cells^[4]. In Vitro:Gliotoxin (50 ng/ml, 48 hours) promotes the internalization of Aspergillus fumigatus by A549 type II human pneumocytes through inducing cofilin phosphorylation and actin cytoskeleton rearrangement^[3].
Gliotoxin (2.5%, 5%, 10%, 20% culture filtrates of Aspergillus fumigatus containing Gliotoxin, 16 hours) induces apoptosis in EL4 thymoma cells through Bak-dependent mechanisms and activation of caspase 3, leading to phosphatidylserine translocation and cell death^[5]. In Vivo:Gliotoxin (50 ng/ml, Intranasal administration, single dose) enhances the invasiveness of Aspergillus fumigatus in Hydrocortisone (HY-N0583)-induced immunosuppressed C57BL/6 mouse models by promoting lung tissue invasion and increasing fungal burden^[3].
Gliotoxin (Intranasal administration, single dose) significantly increases fungal burden in the lungs and mortality in Hydrocortisone (HY-N0583)-induced immunosuppressed BALB/c and 129/Sv mouse models, contributing to the virulence of Aspergillus fumigatus^[4].