Apoptosis trichothecene-induced

Trichothecene-Induced Inflammatory Gene Expression and Apoptosis... 

TRICHOTHECENE-INDUCED INFLAMMATORY GENE EXPRESSION AND APOPTOSIS... 

Islam, Z. et al. Endotoxin potentiation of trichothecene-induced lymphocyte apoptosis is mediated by up-regulation of glucocorticoids. Toxicol. Appl. Pharmacol. 180, 43, 2002. 

Exposure to trichothecenes at levels that partially inhibit translation upregulates expression of many inflammatory and immune-related genes including macrophage, Thl and Th2 cytokines as well as chemokines, cyclooxygenase 2 and inducible nitric oxide synthase.1518 Contrastingly, suppressive effects of trichothecenes on leukocyte function are intimately linked with the induction of apoptosis as has been demonstrated in macrophages, T cells and B cells both in vivo and in vitro.19-20... 

High doses of trichothecenes promote rapid onset of leukocyte apoptosis which likely contributes to immunosuppression. DON and other trichothecenes cause apoptosis in vitro in primary T-cells, B-cells and IgA+ B cells20 as well as HL-60,53 U937 and RAW 264.7 cell lines43 via caspase-mediated mechanisms.54 These in vitro findings are relevant to the intact animal since in vivo administration of trichothecenes to rodents results in apoptosis in thymus, spleen and bone marrow.55-56 Capacity of a trichothecene to induce apoptosis corresponds to ability to inhibit translation.57... 

Shifrin, V. I. and Anderson P. Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis. J. Biol. Chem. 274, 13985, 1999. 

Zhou, H. R. et al. Lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) synergistically induce apoptosis in murine lymphoid organs. Toxicol. Sci. 53, 253, 2000. 

Trichothecenes inhibit synthesis of protein, RNA and DNA as well as mitochondrial and electron transport chain function stimulate lipid peroxidation alter cell membrane function induce apoptosis modulate immune responses activate mitogen-activated protein kinases (MAPKs) and induce gene expression of numerous chemokines and cytokines and alter neurotransmitter levels. 

Experimentally, the macrocyclic trichothecenes satra-toxin G, isosatratoxin F, and roridin A have been shown to cause nasal and pulmonary toxicity when administered intranasally or intratracheally to mice. Intranasal exposure of satratoxin G and roridin A induced apoptosis of olfactory sensory neurons resulting in atrophy of the olfactory epithelium and olfactory nerve layer of the olfactory bulb in the frontal brain (Islam et al, 2006, 2007). Alveolar-type II cells and alveolar macrophages were injured following intratracheal instillation of isosatratoxin F or Stachybotrys spores with marked changes in surfactant synthesis and secretion (Rand et al, 2002). 

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