Inflammatory Modulating Effects of Fungal Molecules on Host Cells

了解宿主细胞激活的机制可能有助于深入了解这些感染的发病机制。我们正在使用不同的靶细胞(即内皮细胞系、淋洗的血液单个核细胞、全血检测)来表征与真菌相关分子(即β-葡聚糖、酵母多糖和海带多糖)相关的早期基因和蛋白表达。 我们已经用免疫分析、针对特定目标基因(即IL-6、8、MCP)的Taq-Man探针以及RT-PCR阵列来评估细胞激活表达，这些阵列允许我们在每个样本中分析84个基因，以评估不同真菌相关分子的相互作用。例如，海带多糖(一种低分子葡聚糖)对单核细胞的刺激与Toll受体途径中抑制和刺激基因表达的混合有关。海带多糖预处理在抑制可得兰(α-β-1，3-葡聚糖)或酵母多糖激活单核细胞方面也有重要作用。我们正在继续使用这些方法评估信号通路，以阐明真菌相关分子激活的宿主炎症机制。

Understanding the mechanisms of host cell activation may provide insight into the pathogenesis of these infections. We are using different target cells (i.e. endothelial cell lines, elutriated blood mononuclear cells, whole blood assays) to characterize the early gene and protein expression associated with fungal- related molecules (i.e. beta glucans, zymosan, and laminarin). We have evaluated the cell activation expression with immunoassays, Taq-Man probes for specific target genes (i.e. IL-6, 8, MCP) as well as RT-PCR arrays which allow us to profile 84 genes per sample to assess the interactions of the different fungal related molecules. For example, stimulation of monocytes with laminarin, a low molecular weight glucan, is associated with a mixture of inhibitory and stimulatory gene expression in the toll receptor pathway. Pretreatment with laminarin also has a major effect on inhibiting monocyte activation by either curdlan (a beta 1,3, glucan) or zymosan. We are continuing to evaluate the signaling pathways using these methodologies in order to elucidate host inflammatory mechanisms activated by fungal related molecules.