Does chronic dietary exposure to the mycotoxin deoxynivalenol affect the porcine hepatic transcriptome when an acute-phase response is initiated through first or second-pass LPS challenge of the liver?

• Published in: Innate immunity (London, England) England), 2021-07, Vol.27 (5), p.388-408
• Main Authors: Dänicke, Sven, Heymann, Ann-Katrin, Oster, Michael, Wimmers, Klaus, Tesch, Tanja, Bannert, Erik, Bühler, Susanne, Kersten, Susanne, Frahm, Jana, Kluess, Jeannette, Kahlert, Stefan, Rothkötter, Hermann-Josef, Billenkamp, Fabian
• Format: Article
• Language: English
• Subjects: Acute-Phase Reaction - genetics; Acute-Phase Reaction - metabolism; Animal Feed; Animals; Apoptosis; B-cell lymphoma; Chemical and Drug Induced Liver Injury - genetics; Chemical and Drug Induced Liver Injury - metabolism; Deoxynivalenol; Diet; Diet - adverse effects; Dietary Exposure; Food Contamination; Gene expression; Inflammation; Lipopolysaccharides; Lipopolysaccharides - metabolism; Liver; Liver - physiology; Lymphocytes B; Lymphocytes T; Mycotoxins; Oligomerization; Original; Swine; TLR4 protein; Toll-like receptors; Transcription; Transcriptome; Transcriptomes; Trichothecenes - toxicity; α-Interferon; γ-Interferon
• ISSN: 1753-4259; 1753-4267
• DOI: 10.1177/17534259211030563

The sensitivity of pigs to deoxynivalenol (DON) might be increased by systemic inflammation (SI), which also has consequences for hepatic integrity. Liver lesions and a dys-regulated gene network might hamper hepatic handling and elimination of DON whereby the way of initiation of hepatic inflammation might play an additional role. First and second-pass exposure of the liver with LPS for triggering a SI was achieved by LPS infusion via pre- or post-hepatic venous route, respectively. Each infusion group was pre-conditioned either with a control diet (0.12 mg DON/kg diet) or with a DON-contaminated diet (4.59 mg DON/kg diet) for 4 wk. Liver transcriptome was evaluated at 195 min after starting infusions. DON exposure alone failed to modulate the mRNA expression significantly. However, pre- and post-hepatic LPS challenges prompted transcriptional responses in immune and metabolic levels. The mRNAs for B-cell lymphoma 2-like protein 11 as a key factor in apoptosis and IFN-γ released by T cells were clearly up-regulated in DON-fed group infused with LPS post-hepatically. On the other hand, mRNAs for nucleotide binding oligomerization domain containing 2, IFN-α and eukaryotic translation initiation factor 2α kinase 3 as ribosomal stress sensors were exclusively up-regulated in control pigs with pre-hepatic LPS infusion. These diverse effects were traced back to differences in TLR4 signalling.