Department of Biology, Saint Mary's University, 923 Robie St, Halifax, NS, B3H 3C3, Canada,
Arch Toxicol. 2013 Oct;87(10):1841-50. doi: 10.1007/s00204-013-1042-4. Epub 2013 Mar 30.
People living in damp buildings are typically exposed to spore and mycelial fragments of the fungi that grow on damp building materials. There is experimental evidence that this exposure to triple-helical (1, 3)-β-D glucan and low molecular weight toxins may be associated with non-atopic asthma observed in damp and moldy buildings. However, the mechanisms underlying this response are only partially resolved. Using the pure (1, 3)-β-D glucan, curdlan, and the murine macrophage cell line, RAW 264.7, there were two objectives of this study. The first was to determine whether signal transduction pathways activating asthma-associated cell signaling pathways were stimulated using mouse transduction Pathway Finder(®) arrays and quantitative real-time (QRT) PCR. The second objective was to evaluate the dose and temporal responses associated with transcriptional changes in asthma-associated cytokines, the signal transduction receptor gene Dectin-1, and various transcription factor genes related to the induction of asthma using customized RT-PCR-based arrays. Compared to controls, the 10(-7) M curdlan treatment induced significant changes in gene transcription predominately in the NFkB, TGF-β, p53, JAK/STAT, P13/AKT, phospholipase C, and stress signaling pathways. The 10(-8) M curdlan treatment mainly induced NFkB and TGF-β pathways. Compared to controls, curdlan exposures also induced significant dose- and time-dependent changes in the gene translations. We found that that curdlan as a non-allergenic potentiator modulates a network of transduction signaling pathways not only associated with TH-1, TH-2, and TH-3 cell responses including asthma potentiation, but a variety of other cell responses in RAW 264.7 cells. These results help provide mechanistic basis for some of the phenotypic changes associated with asthma that have been observed in in vitro, in vivo, and human studies and open up a hypothesis-building process that could explain the rise of non-atopic asthma associated with fungi.
居住在潮湿建筑物中的人们通常会接触到在潮湿建筑材料上生长的真菌的孢子和菌丝片段。有实验证据表明，这种暴露于三螺旋（1,3）-β-D 葡聚糖和低分子量毒素可能与在潮湿和发霉的建筑物中观察到的非特应性哮喘有关。然而，这种反应的机制仅部分得到解决。本研究使用纯（1,3）-β-D 葡聚糖、几丁质和鼠巨噬细胞系 RAW 264.7，有两个目的。第一个目的是确定使用小鼠转导途径查找器（®）阵列和定量实时（QRT）PCR 是否刺激激活与哮喘相关的细胞信号转导途径的信号转导途径。第二个目的是评估与哮喘相关细胞因子、信号转导受体基因 Dectin-1 以及与哮喘诱导相关的各种转录因子基因转录变化相关的剂量和时间反应，使用基于定制 RT-PCR 的阵列。与对照组相比，10(-7) M 几丁质处理主要诱导 NFkB、TGF-β、p53、JAK/STAT、P13/AKT、磷脂酶 C 和应激信号通路中基因转录的显著变化。10(-8) M 几丁质处理主要诱导 NFkB 和 TGF-β 途径。与对照组相比，几丁质暴露还诱导基因翻译的显著剂量和时间依赖性变化。我们发现，几丁质作为一种非变应原增强剂，不仅调节与 TH-1、TH-2 和 TH-3 细胞反应（包括哮喘增强）相关的转导信号通路网络，而且还调节 RAW 264.7 细胞中的各种其他细胞反应。这些结果有助于为一些与哮喘相关的表型变化提供机制基础，这些变化在体外、体内和人类研究中都有观察到，并为解释与真菌相关的非特应性哮喘的上升提供了一个假设构建过程。
