title: T-2 toxin is a cytochrome P450 1A1 inducer and leads to MAPK/p38- but not aryl hydrocarbon receptor-dependent interleukin-8 secretion in the human intestinal epithelial cell line Caco-2.
abstract: T-2 toxin (T-2) is a secondary metabolite produced by various mould species of the genus Fusarium and a common contaminant detectable in staple foods of cereal origin. In the present study the impact of this mycotoxin on the inflammatory response of the intestinal epithelial cell line Caco-2 was examined by measuring interleukin (IL)-8 secretion. A T-2 concentration dependent IL-8 up-regulation was detected in IL-1β stimulated and unstimulated Caco-2 cells. To elucidate the possible underlying molecular mechanism of this conditional T-2-provoked IL-8 induction, a possible involvement of the aryl hydrocarbon receptor (AHR) and the mitogen-activated protein kinase (MAPK) pathway was investigated. Like benzo-[a]-pyrene (B[a]P), a well known AHR ligand, T-2 led to cytochrome P450 1A1 (CYP1A1) mRNA expression in Caco-2 cells, which could be inhibited by the AHR antagonist resveratrol. However, resveratrol did not influence T-2-dependent IL-8 induction. Since T-2 did not lead to AHR-translocation in stably GFP-AHR-transfected cells, an AHR dependency of T-2-triggered IL-8 induction could be excluded. But finally, up to a total inhibition of T-2-induced IL-8 was obtained using p38 inhibitors. Therefore, we conclude that p38 MAPK is responsible for mediating the inflammatory properties of the type A trichothecene T-2.
authors: UFZ-Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig, Germany.
authors: Pierre
authors: P
authors: Kruber
authors: Saskia
authors: S
authors: Trump
authors: Johann
authors: J
authors: Behrens
authors: Irina
authors: I
authors: Lehmann
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013605:T-2 Toxin / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology
chemical_list: D016209:Interleukin-8; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D048051:p38 Mitogen-Activated Protein Kinases; D013605:T-2 Toxin