Prolonged exposure to mycotoxins, even in subtoxic concentrations, might contribute to modulate pro- or anti-inflammatory cascades and ultimately have long-term consequences on our health. In line, there is an increasing need to describe and comprehend the potential immunomodulatory effects of toxins that can be produced from fungi proliferating even in a domestic environment like, for instance, Alternaria alternata. Taking this as a starting point, we investigated the effects of one of the most potent genotoxic compounds produced by this fungi type, namely altertoxin II (ATXII) on THP-1 macrophages. In noncytotoxic concentrations (0.1-1 μM), ATXII inhibited the activation of the transcription factor NF-κB, and this event was accompanied by significant mitochondrial superoxide production (1 μM ATXII). Both responses seemed dependent on membrane structure and morphology since they were modulated by the coincubation with the cholesterol complexing agent methyl-β-cyclodextrin (MβCD, 10-50 μM). Moreover, toxicity of ATXII was enhanced by cholesterol load (cholesterol-MβCD). The mycotoxin induced also lipid peroxidation (1-10 μM, ATXII) possibly streaming down at the mitochondrial level and suppressing NF-κB activation in THP-1 macrophages.

中文翻译：

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霉菌毒素替代毒素II诱导脂质过氧化反应，连接THP-1巨噬细胞中的线粒体应激响应NF-κB抑制。

长时间暴露于霉菌毒素，即使处于亚毒性浓度，也可能有助于调节促炎或抗炎反应，最终对我们的健康产生长期影响。一致地，越来越需要描述和理解毒素的潜在免疫调节作用，这些毒素甚至在家庭环境中，例如在链格孢（Alternaria alternata）中也可以从真菌的繁殖中产生。以此为出发点，我们研究了这种真菌类型产生的最有效的遗传毒性化合物之一，即互毒素II（ATXII）对THP-1巨噬细胞的影响。在非细胞毒性浓度（0.1-1μM）中，ATXII抑制了转录因子NF-κB的激活，并且此事件伴随着线粒体超氧化物的大量产生（1μMATXII）。这两种反应似乎都取决于膜的结构和形态，因为它们是通过与胆固醇络合剂甲基-β-环糊精（MβCD，10-50μM）共孵育调节的。此外，胆固醇负荷（胆固醇-MβCD）可增强ATXII的毒性。霉菌毒素还诱导脂质过氧化（1-10μM，ATXII），可能在线粒体水平下流并抑制THP-1巨噬细胞中的NF-κB活化。