基础与临床研究表明，ICAM-1和IL-8过度表达与急性肺损伤的发生密切相关。申请人前期研究表明，Tristetraprolin（TTP）在mRNA水平调控了ICAM-1和IL-8表达，但TTP如何介导mRNA降解尚不清楚。有研究发现CAF1能导致mRNA脱腺苷而降解，而TTP能与CAF1结合。申请人推测TTP可能同时与目标mRNA和CAF1结合，通过CAF1导致目标mRNA脱腺苷而降解，即：TTP通过CAF1调控了ICAM-1和IL-8表达，并影响急性肺损伤的发生发展。为验证这一假说，我们将通过肺微血管内皮细胞和基因敲除小鼠模型，采用Western blot、PCR及病理检测等手段，从RNA、分子和动物水平探讨CAF1在TTP调控ICAM-1和IL-8表达中的作用及其对急性肺损伤的影响。本研究对于揭示炎症介质ICAM-1和IL-8表达的调控机制有重要意义，为临床防治急性肺损伤提供新思路。

Over expression of ICAM-1 and IL-8 leads to the development of acute lung injury according to the laboratory and clinical studies. Our previous study revealed that Tristetraprolin (TTP) regulates ICAM-1 and IL-8 expression at mRNA level. But the regulatory mechanism of ICAM-1 and IL-8 expression remains unclear. A previous study showed that CAF1, which could bind to TTP, causes mRNA deadenylation and decay. We propose that TTP regulates ICAM-1 and IL-8 expression via CAF1 and eventually affect the development of acute lung injury. To determine this hypothesis, we will use pulmonary microvascular endothelia cells and CAF1-knockout mice models and western blot, real time PCR and pathology methods to investigate the role of CAF1 in the regulation of ICAM-1 and IL-8 expression by TTP at RNA, molecular and in vivo levels. This study will be very important in revealing the mechanism of ICAM-1 and IL-8 expression during acute lung injury, which will provide a new strategy for the effective management of acute lung injury.