title: Comparative study of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol on intestinal transport and IL-8 secretion in the human cell line Caco-2.
abstract: The effects of the trichothecene mycotoxin deoxynivalenol (DON) and its acetylated derivatives, 3-acetyldeoxynivalenol (3ADON) and 15-acetyldeoxynivalenol (15ADON) on human intestinal cell Caco-2 were investigated by the studies of transepithelial transport, gene expression, and cytokine secretion. Permeability across a Caco-2 cell monolayer was evaluated by transport study. Transport rates were ranked as DON, 3ADON<15ADON in apical-basolateral direction. 15ADON showed the highest permeability, induced the highest decrease in transepithelial electrical resistance (TEER), and prompted significant Lucifer Yellow permeability. These results showed that 15ADON affect paracellular barrier function extremely. In addition, gene expressions induced by toxins were screened by DNA microarray for investigating cellular effect on Caco-2 cell. The most remarkable gene induced by DON and 15ADON was inflammatory chemokine IL-8 and thus mRNA expression and secretion of IL-8 were analyzed by PCR and ELISA. Both DON and acetylated DONs could induce mRNA expression and production of IL-8. In particular, ELISA assay showed that the ability to produce IL-8 was ranked as 3ADON<DON<15ADON. Our results indicated that 15ADON caused the highest permeability and highest IL-8 secretion among DON, 3ADON, and 15ADON in human intestinal cell.
authors.affiliation: Central Laboratories for Key Technologies, Research & Development Division, Kirin Company, Limited, 1-13-5, Fukuura Kanazawa-ku, Yokohama 236-0004, Japan. Tomoyuki_Kadota@kirin.co.jp
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kadota
authors.forename: Hiroko
authors.initials: H
authors.lastname: Furusawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirano
authors.forename: Osamu
authors.initials: O
authors.lastname: Tajima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kamata
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sugita-Konishi
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014255:Trichothecenes / Q000494:pharmacology*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D014255:Trichothecenes; C043247:3-acetyldeoxynivalenol; C046760:15-acetyldeoxynivalenol; C007262:deoxynivalenol
keywords: Acetyldeoxynivalenol; Caco-2 cells; IL-8; Transepithelial transport; Trichothecene