TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 背景资料：长时间喂食硬蜱，加上细菌传播，应会导致吸血部位出现强烈的炎症反应。然而，蜱唾液中存在的因素可能会下调这种有害的反应。为了保持进食成功，蜱需要在唾液中含有抗炎和免疫抑制成分。在宿主体内，激活的单核细胞在整个体内循环，传播病原体和载体（蜱唾液）的作用。这些细胞在免疫防御和炎症中发挥重要作用。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：蜱唾液，在B的背景下。伯氏（Bb）传播，可以对与单核细胞/巨噬细胞相关的炎症途径的表达具有广泛的影响。本研究旨在确定蜱唾液对与Bb共培养的人单核细胞基因表达的体外影响。 研究方法：在存在或不存在蜱唾液的情况下，在四个时间点（30分钟、2小时、12小时和24小时），从用Bb刺激的人THP-1单核细胞分离的RNA转录物用于使用人寡核苷酸阵列分析全局基因表达。基于显著性（P等于或小于0.05）和幅度（等于或大于2倍）鉴定差异表达者。免疫途径分析用于研究受影响基因的功能，生物学过程，途径和网络相互作用。结果如下：唾液可对某些促炎介质（如IL-8）的表达具有抑制作用，以及对特定分子（如IL-10 RA、IL-4 r、IL 5 r和SOCS家族）具有刺激作用。结论：微阵列的结果可以提供一个广泛的观点单核细胞代谢途径和家族的基因受蜱唾液在与Bb共培养。

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.