Department of Civil and Environmental Engineering, Duke University, Durham, North Carolina 27708-0287, United States.
Environ Toxicol. 2013 Jan;28(1):51-60. doi: 10.1002/tox.20698. Epub 2011 Mar 7.
Very little is known about the mechanisms that occur in human cells upon exposure to fungi as well as their mycotoxins. A better understanding of toxin-regulated gene expression would be helpful to identify safe levels of exposure and could eventually be the basis for establishing guidelines for remediation scenarios following a water intrusion event. In this research, cytokine mRNA expression patterns were investigated in the human monocytic THP-1 cell line exposed to fungal extracts of various fragment sizes obtained from Stachybotrys chartarum RTI 5802 and/or Aspergillus versicolor RTI 3843, two common and well-studied mycotoxin producing fungi. Cytokine mRNA expression was generally upregulated 2-10 times following a 24 h exposure to fungal extracts. Expression of the proinflammatory interleukin-1β, interleukin-8, and tumor necrosis factor-α genes increased while the anti-inflammatory gene interleukin-10 also increased albeit at very low level, suggesting that negative feedback regulation mechanism of production of proinflammatory cytokines initiated upon 24 h of incubation. In addition, submicron size extracts of A. versicolor caused significant death of THP-1 cells, whereas extracts of S. chartarum caused no cell death while the mixture of the two fungi had an intermediate effect. There was no general correlation between gene expression and fragment sizes, which suggests that all submicron fragments may contribute to inflammatory response.
目前对于人类细胞暴露于真菌及其霉菌毒素时所发生的机制知之甚少。更好地了解毒素调控基因表达将有助于确定安全暴露水平,最终可能成为建立水入侵事件后修复场景指南的基础。在这项研究中,研究了人单核细胞 THP-1 细胞系在暴露于来自石壶藻 RTI 5802 和/或黄曲霉 RTI 3843 的各种大小片段的真菌提取物后细胞因子 mRNA 表达模式,这两种真菌是常见且研究充分的产霉菌毒素真菌。在暴露于真菌提取物 24 小时后,细胞因子 mRNA 的表达通常上调 2-10 倍。促炎细胞因子白细胞介素-1β、白细胞介素-8 和肿瘤坏死因子-α基因的表达增加,而抗炎基因白细胞介素-10 也增加,尽管水平非常低,这表明在孵育 24 小时后启动了促炎细胞因子产生的负反馈调节机制。此外,黄曲霉的亚微米大小提取物会导致 THP-1 细胞明显死亡,而石壶藻的提取物则不会导致细胞死亡,而两种真菌的混合物则具有中间作用。基因表达与片段大小之间没有普遍相关性,这表明所有亚微米片段都可能导致炎症反应。