Inflammatory Modulating Effects of Fungal Molecules on Host Cells

了解宿主细胞激活的机制可能会提供深入了解这些感染的发病机制。我们使用不同的靶细胞（即内皮细胞系、淘析的血液单核细胞、全血测定）来表征与真菌相关分子（即β葡聚糖、酵母聚糖和海带多糖）相关的早期基因和蛋白质表达。 我们已经用免疫测定、针对特定靶基因（即IL-6、8、MCP）的Taq-Man探针以及RT-PCR阵列评估了细胞活化表达，RT-PCR阵列允许我们对每个样品的84个基因进行分析以评估不同真菌相关分子的相互作用。例如，用海带多糖（一种低分子量葡聚糖）刺激单核细胞与toll受体途径中抑制性和刺激性基因表达的混合物有关。用海带多糖预处理也对可得兰（β 1，3，葡聚糖）或酵母聚糖抑制单核细胞活化具有重要作用。我们将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.