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Comparison of the cytokine and chemokine dynamics of the early inflammatory response in models of burn injury and infection.

机译:在烧伤和感染模型中早期炎症反应的细胞因子和趋化因子动力学的比较。

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摘要

The inflammatory response, and its subsequent resolution, are the result of a very complex cascade of events originating at the site of injury or infection. When the response is severe and persistent, Systemic Inflammatory Response Syndrome can set in, which is associated with a severely debilitating systemic hypercatabolic state. This complex behavior, mediated by cytokines and chemokines, needs to be further explored to better understand its systems properties and potentially identify multiple targets that could be addressed simultaneously. In this context, short term responses of serum cytokines and chemokines were analyzed in two types of insults: rats receiving a "sterile" cutaneous dorsal burn on 20% of the total body surface area (TBSA); rats receiving a cecum ligation and puncture treatment (CLP) to induce infection. Considering the temporal variability observed in the baseline corresponding to the control group, the concept of area under the curve (AUC) was explored to assess the dynamic responses of cytokines and chemokines. MCP-1, GROK/KC, IL-12, IL-18 and IL-10 were observed in both burn and CLP groups. While IL-10 concentration was only increased in the burn group, Eotaxin was only elevated in CLP group. It was also observed that Leptin and IP-1 concentrations were decreased in both CLP and sham-CLP groups. The link between the circulating protein mediators and putative transcription factors regulating the cytokine/chemokine gene expression was explored by searching the promoter regions of cytokine/chemokine genes in order to characterize and differentiate the inflammatory responses based on the dynamic data. Integrating multiple sources together with the bioinformatics tools identified mediators sensitive to type and extent of injury, and provided putative regulatory mechanisms. This is essential to gain a better understanding for the important regulatory points that can be used to modulate the inflammatory state at molecular level.
机译:炎症反应及其随后的消退是源自损伤或感染部位的一系列非常复杂的事件的结果。当反应严重且持续时,可出现全身性炎症反应综合症,这与严重破坏全身的高分解代谢状态有关。需要进一步探索这种由细胞因子和趋化因子介导的复杂行为,以更好地了解其系统特性并潜在地确定可以同时解决的多个靶标。在这种情况下,分析了两种类型的侮辱对血清细胞因子和趋化因子的短期反应:大鼠在全身表面积(TBSA)的20%处接受“无菌”皮肤背侧烧伤;大鼠接受盲肠结扎和穿刺治疗(CLP)诱导感染。考虑到在与对照组相对应的基线中观察到的时间变异性,探索了曲线下面积(AUC)的概念以评估细胞因子和趋化因子的动态响应。在烧伤组和CLP组均观察到MCP-1,GROK / KC,IL-12,IL-18和IL-10。 IL-10浓度仅在烧伤组中升高,而嗜酸性粒细胞趋化因子仅在CLP组中升高。还观察到在CLP和假-CLP组中,瘦素和IP-1浓度均降低。通过搜索细胞因子/趋化因子基因的启动子区域来探索循环蛋白介体和调节细胞因子/趋化因子基因表达的假定转录因子之间的联系,以基于动态数据表征和区分炎症反应。将多种来源与生物信息学工具整合在一起,可以确定对伤害类型和程度敏感的介体,并提供推定的调节机制。这对于更好地理解可用于在分子水平上调节炎症状态的重要调节点至关重要。

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