Aflatoxins B1, B2 and G1 modulate cytokine secretion and cell surface marker expression in J774A.1 murine macrophages

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 B1 (AFB1), aflatoxin B2 (AFB2) and aflatoxin G1 (AFG1) 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 0.1 ng/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 AFB1 or AFB2 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.

► Studied the effect of AFB1, AFB2 and AFG1 on murine macrophages.
► Analyzed the change in cytokine secretion and cell surface marker expression.
► Significant change in CD14 and TLR2 expression.
► Significant change in pro-inflammatory cytokine secretion.
► Results were isoform specific.