TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：硬蜱的长期摄食，再加上细菌的传播，应该会在摄血部位引起强烈的炎症反应。然而，扁虱唾液中存在的因素可能会下调这种有害的反应。为了维持摄食成功，扁虱需要唾液中含有抗炎和免疫抑制成分。在宿主中，激活的单核细胞循环，分布病原体和媒介(扁虱唾液)的影响。这些细胞在免疫防御和炎症中发挥着重要作用。单核细胞产生促炎介质，如IL-8，一种控制炎症和免疫细胞流入的趋化因子，以及IL-6，一种关键的B细胞分化因子。假设：在伯氏杆菌(BB)传播的背景下，扁虱唾液可以对与单核/巨噬细胞相关的炎症途径的表达产生广泛的影响。本研究的目的是在体外研究壁虱唾液对与BB共培养的人单核细胞基因表达的影响。方法：从人THP-1单核细胞中提取RNA转录物，利用人寡核苷酸芯片分析在有或没有扁虱唾液的情况下，4个时间点(30分钟、2小时、12小时和24小时)的THP-1单核细胞的整体基因表达。根据显着性(P等于或小于0.05)和大小(等于或大于2倍)确定差异表达者。独创性途径分析被用来研究受影响基因的功能、生物学过程、途径和网络相互作用。结果：唾液对IL-8等促炎介质的表达有抑制作用，对IL-10RA、IL-4r、IL5R和SOCS家族等特异性分子有刺激作用。结论：基因芯片结果可以为单核细胞代谢途径和在与BB共培养过程中受壁虱唾液影响的基因家族提供广阔的前景。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: The prolonged feeding of ixodid ticks, in combination with bacterial transmission should lead to a robust inflammatory response at the blood-feeding site. Yet, factors present in tick saliva may down-regulate such deleterious responses. To maintain feeding success, ticks require anti-inflammatory and immunosuppressive elements in their saliva. In the host, activated monocytes circulate throughout, distributing the effects of both pathogen and vector (tick saliva). These cells play important roles in immune defense and inflammation. Monocytes produce pro-inflammatory mediators such as IL-8, a chemokine that controls the influx of inflammatory and immune cells, and IL-6, a key B-cell differentiation factor. Hypothesis: Tick saliva, in the context of B. burgdorferi (Bb) transmission, can have widespread effects on the expression of inflammatory pathways associated with monocytes/macrophages. This study aims to identify the in vitro effects of tick saliva on human monocyte gene expression co-cultured with Bb. Methods: RNA transcripts isolated from Human THP-1 monocytes stimulated with Bb in the presence or absence of tick saliva, at four time points (30-min, 2-hr, 12-hr, and 24-hr) were used to profile global gene-expression, using human oligonucleotide arrays. Differential expresser's were identified based on significance (P equal to or less than 0.05) and magnitude (equal to or greater than 2-fold). Ingenuity Pathways Analysis was used to investigate the function, biological processes, pathways, and network interactions of the affected genes. Results: Saliva can have a suppressive effect on the expression of certain pro-inflammatory mediators, such as IL-8, as well as have a stimulatory effect on specific molecules such as IL-10RA, IL-4r, IL5r and the SOCS family. Conclusions: Microarray results can provide a broad perspective on monocytic metabolic pathways and families of genes affected by tick saliva during co-culture with Bb.