Interactions of deoxynivalenol and lipopolysaccharides on cytokine excretion and mRNA expression in porcine hepatocytes and Kupffer cell enriched hepatocyte cultures.
The effects of deoxynivalenol (DON) on the mRNA expression of cytokines and inflammation-related genes, as well as the cytokine secretion of porcine hepatocytes and Kupffer cell enriched hepatocyte cultures (co-cultures), were investigated in the absence or presence of LPS. DON and LPS acted in a synergistic manner with regard to a significantly increased mRNA expression of TNF-alpha in hepatocytes exposed to 500 nM or 2000 nM DON, or non-significant increase in co-cultures after 3h of exposure. TNF-alpha supernatant concentrations were increased due to LPS but did not reflect the synergistic effects with DON as observed at mRNA level. IL-6 mRNA in hepatocyte cultures at 6h paralleled the TNF-alpha supernatant pattern at this time point. In co-cultures and hepatocytes, a DON dose dependent induction of IL-6 mRNA was detected in cells not exposed to LPS. Supernatant concentrations of LPS-induced IL-6 were significantly decreased by 2000 nM DON in both types of cell cultures. Also the mRNA expression of the anti-inflammatory IL-10 was increased by DON to various degrees depending on DON-dose, stimulation with LPS and time point of measurement. After 6h, expression of iNOS was only induced by 2000 nM DON, but not in LPS treated cells. Even if mRNA induction was not paralleled by related supernatant concentrations of TNF-alpha, IL-6 and IL-10 under the conditions of the present investigations, it was clearly demonstrated that DON has the potential to provoke and modulate immunological reactions of porcine liver cells.
Döll
Susanne
S
Division of Veterinary Pharmacology, Pharmacy and Toxicology, Department of Equine Science, Faculty of Veterinary Medicine, Utrecht University, The Netherlands. susanne.doell@fli.bund.de
Schrickx
Jan A
JA
Dänicke
Sven
S
Fink-Gremmels
Johanna
J
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D013552:Swine; D014255:Trichothecenes / Q000633:toxicity*
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014255:Trichothecenes; C440499:lipopolysaccharide, Escherichia coli O111 B4; C007262:deoxynivalenol