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Aflatoxins B(1), B(2) and G(1) modulate cytokine secretion and cell surface marker expression in J774A.1 murine
Johanna C Bruneau1, Edwina Stack, Richard O'Kennedy
1Applied Biochemistry Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland. johanna.bruneau@gmail.com
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.
Insights
Aflatoxins, fungal toxins in food, suppress immune responses. Low-dose exposure altered cytokine secretion, decreasing interleukin-10 and increasing interleukin-6, while affecting key immune cell surface markers.
Area of Science:
- Immunology
- Toxicology
- Mycology
Background:
- Aflatoxins are toxic fungal metabolites found in food and feed.
- They are known hepatocarcinogens and immunosuppressants.
- Understanding their immunomodulatory mechanisms is crucial.
Purpose of the Study:
- To investigate the effects of aflatoxin B1, B2, and G1 on cytokine secretion in murine macrophages.
- To examine alterations in immune cell surface marker expression following aflatoxin exposure.
- To elucidate the mechanisms of aflatoxin-induced immunosuppression.
Main Methods:
- Murine macrophage cell line (J774A.1) exposed to varying doses of aflatoxins (AFB1, AFB2, AFG1).
- Cytokine secretion (IL-10, IL-6) measured after lipopolysaccharide (LPS) stimulation.
- Expression levels of Toll-like receptors (TLR2, TLR4) and CD14 analyzed.
Main Results:
- Low-dose aflatoxin exposure significantly altered cytokine profiles.
- Decreased secretion of anti-inflammatory interleukin-10 (IL-10) observed.
- Increased secretion of pro-inflammatory interleukin-6 (IL-6) noted.
- Significant reduction in Toll-like receptor 2 (TLR2) and CD14 expression.
Conclusions:
- Aflatoxins modulate host immune responses through cytokine imbalance.
- Alterations in cytokine secretion and cell surface markers contribute to immunosuppression.
- Further research into aflatoxin immunotoxicity is warranted.
