title: Aflatoxins B(1), B(2) and G(1) modulate cytokine secretion and cell surface marker expression in J774A.1 murine macrophages.
abstract: Aflatoxins are fungal products which occur in food and feed. They are potent hepatocarcinogens, and are known to cause immunosuppression. We investigated the effect of aflatoxin B(1) (AFB(1)), aflatoxin B(2) (AFB(2)) and aflatoxin G(1) (AFG(1)) exposure, alone and in combination, on the secretion of key pro- and anti-inflammatory cytokines from the murine macrophage cell line, J774A.1. Exposure of macrophages to low doses of aflatoxin (0.01 or 0.1ng/mL) resulted in a statistically significant change in the secretion of a number of cytokines following stimulation with lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls. Specifically, treatment with AFB(1) or AFB(2) alone significantly decreased (P<0.01) the secretion of the anti-inflammatory cytokine interleukin (IL) 10 (IL-10), while the secretion of the pro-inflammatory cytokine IL-6 was significantly increased (P<0.01). In addition, aflatoxin exposure affected expression levels of key cell surface markers involved in the inflammatory response. Toll-like receptor 2 (TLR2) and Cluster of Differentiation 14 (CD14) expression levels decreased significantly (P<0.01), but Toll-like receptor 4 (TLR4) expression was unaffected. This data provides further insight into the mechanisms by which aflatoxins modulate the host immune response to exert their immunosuppressive activity.
authors.affiliation: Applied Biochemistry Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland. johanna.bruneau@gmail.com
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bruneau
authors.forename: Edwina
authors.initials: E
authors.lastname: Stack
authors.forename: Richard
authors.initials: R
authors.lastname: O'Kennedy
authors.forename: Christine E
authors.initials: CE
authors.lastname: Loscher
mesh_terms: D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000633:toxicity*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000348:Aflatoxins; D002273:Carcinogens; D016207:Cytokines; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4