Patulin, Deoxynivalenol, Zearalenone and T-2 Toxin Affect Viability and Modulate Cytokine Secretion in J774A.1 Murine Macrophages

Abstract

Mycotoxins are secondary fungal metabolites, which occur in food and feed. They have detrimental effects on the health of humans and animals, and they are known to cause immunosuppression. In this study the effect of patulin, deoxynivalenol (DON), zearalenone (ZEN) and T-2 toxin exposure on the viability and the secretion of key pro-and anti-inflammatory cytokines from the murine macrophage cell line, J774A.1, was investigated. Exposure of macrophages to high doses of ZEN (100,000 pg/mL) and T-2 toxin (10,000 and 100,000 pg/mL) resulted in a significant decrease (P < 0.05 and P < 0.01) in cell viability. Exposure of macrophages to these mycotoxins resulted in a dose-dependent modulation of cytokine secretion. Specifically, exposure to low doses of patulin (0.001, 0.1 and 1 pg/mL) resulted in a statistically significant decrease in the secretion of the pro-inflammatory cytokines interleukin (IL) 6 (IL-6) and tumor necrosis factor alpha (TNF-α), following stimulation with lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls. Treatment with low doses of DON (0.001 pg/mL) and ZEN (0.001 and 0.01 pg/mL) significantly decreased (P < 0.01) the secretion of the pro-inflammatory cytokine IL-12p40, while several doses of T-2 toxin (0.001, 0.01, 0.1, 1 and 100 pg/mL) caused a significant decrease the expression of IL-6. Each of the mycotoxins also significantly increased the production of the anti-inflammatory cytokine IL-10, both before and after LPS stimulation. This data provides further insight into the mechanisms by which mycotoxins modulate the host immune response to exert their immunosuppressive activity.

T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line

“…Quantitative cell viability assays using CCK-8 showed that T-2 toxin inhibited proliferation of HL-7702 cells in a dose-dependent manner after a 24 h exposure and exhibited cytotoxic response. The present result was consistent with other previous studies [33][34][35].…”

Fungal Toxins and Host Immune Responses

“…Moreover, rats that received 0.1 mg/kg (body weight) of patulin per day displayed mitochondrial abnormalities after 60 days and an increase in the production of apoptotic bodies after 90 days (Özsoy et al, 2008). LPS-stimulated J774A.1 murine macrophages treated with 0.0065-6.5 pM patulin exhibited reduced secretion of IL-6 and TNF-α in vitro (Loftus et al, 2016), while LPSdependent production of IL-6 and NO was blocked in RAW264.7 macrophages in response to 5-100 µM patulin and cell viability was markedly reduced at concentrations above 50 µM in vitro (Tsai et al, 2016). Furthermore, the induction of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) and pro-IL-1β in LPS-primed J774.1 macrophages was reduced by patulin, suggesting that inflammasome responses are also negatively affected (Tsai et al, 2016).…”