title: Deoxynivalenol and satratoxin G potentiate proinflammatory cytokine and macrophage inhibitory protein 2 induction by Listeria and Salmonella in the macrophage.
abstract: Health risks from microbial pathogens and toxins encountered in food and the environment continue to be of worldwide concern. The purpose of this research was to test the hypothesis that trichothecene mycotoxins amplify inflammatory responses to foodborne bacterial pathogens. We assessed the capacity of deoxynivalenol (DON) and satratoxin G (SG) to potentiate chemokine and proinflammatory cytokine production in RAW 264.7 murine macrophages induced by Listeria monocytogenes and Salmonella Typhimurium. When macrophage cultures were incubated with killed irradiated suspensions of the pathogens for 24 h, the minimum Listeria concentrations for induction of macrophage inhibitory protein 2 (MIP-2), interleukin-1beta (IL-beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) were 0.01, 0.01, 1.0, and 1.0 microg/ml (P < 0.05) and the minimum Salmonella concentrations were 0.01, 0.01, 0.1, and 0.1 microg/ml, respectively (P < 0.05). Induction of all four mediators by both pathogens was potentiated by DON (at 100 and 250 ng/ml); observed responses were significantly higher than predicted additive responses (P < 0.05). SG (at 2 and 5 ng/ml) also significantly amplified induction of IL-1beta and TNF-alpha (P < 0.05) by both Listeria and Salmonella. These results indicate that DON encountered in Fusarium-contaminated food and SG from Stachybotrys-contaminated indoor environments could magnify innate inflammatory responses to foodborne bacterial pathogens.
authors.affiliation: Department of Food Science and Human Nutrition and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: E
authors.initials: E
authors.lastname: Mbandi
authors.forename: J J
authors.initials: JJ
authors.lastname: Pestka
mesh_terms: D000818:Animals; D002460:Cell Line; D054426:Chemokine CXCL2; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6; D008070:Lipopolysaccharides / Q000494:pharmacology; D008087:Listeria / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D015846:Monokines / Q000378:metabolism*; D009183:Mycotoxins / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015846:Monokines; D009183:Mycotoxins; D014255:Trichothecenes; D014409:Tumor Necrosis Factor-alpha; C028268:satratoxin G; C007262:deoxynivalenol