title: Deoxynivalenol-induced cytotoxicity, cytokines and related genes in unstimulated or lipopolysaccharide stimulated primary porcine macrophages.
abstract: The cytotoxicity of deoxynivalenol (DON) as well as the induction of cytokines and related genes was investigated in porcine pulmonary alveolar macrophages (PAM) in absence or presence of lipopolysaccharides (LPS). IC(20) values were 1.1, 0.4 and 1.0microM DON in the MTT, neutral red and alamar blue assay, respectively, and did not differ significantly in the presence of LPS. The mRNA expression of tumour necrosis factor (TNF)-alpha peaked at 3h, whereas LPS and DON showed synergistic effects resulting in an approximately 20-fold increase at 500nM DON as compared to untreated controls. The supernatant concentrations of TNF-alpha showed similar synergistic effects. The expression of interleukin (IL)-1beta was significantly induced by DON (except for 12h) and LPS. An induction of the mRNA expression of IL-6 by DON was evident only at 3h, whereas the supernatant concentrations of LPS stimulated PAM incubated with 500nM DON were significantly decreased at most time points. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression did not seem to contribute to the effects of DON in porcine macrophages. The results of the present investigation suggest a contribution of cytokines, especially TNF-alpha and IL-1beta, induced by DON in porcine macrophages to the effects observed in vivo.
authors.affiliation: Department of Equine Science, Utrecht University, The Netherlands. susanne.doell@fli.bund.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Döll
authors.forename: Jan A
authors.initials: JA
authors.lastname: Schrickx
authors.forename: Sven
authors.initials: S
authors.lastname: Dänicke
authors.forename: Johanna
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014255:Trichothecenes / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014255:Trichothecenes; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; C007262:deoxynivalenol