The molecular fingerprint of lung inflammation after blunt chest trauma.
The molecular fingerprint of lung inflammation after blunt chest trauma.
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DOI：
10.1186/s40001-015-0164-y
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发表时间：
2015-08-25
影响因子：
4.2
通讯作者：
Huber-Lang M
中科院分区：
文献类型：
--
作者：
Ehrnthaller C;Flierl M;Perl M;Denk S;Unnewehr H;Ward PA;Radermacher P;Ignatius A;Gebhard F;Chinnaiyan A;Huber-Lang M
严重钝性胸部创伤后，急性肺损伤（ALI）的发展往往与严重甚至致命的并发症有关。特别是在钝性胸部创伤后的多发伤患者中，ALI/ARDS [急性呼吸窘迫综合征（ARDS）]是常见的。然而，在最初的创伤后阶段，炎症临床体征往往不明显，基因表达谱的潜在变化是未知的。因此，在明确的双侧肺损伤模型中表征了钝性胸部创伤后肺组织中的炎症。使用代表9240个基因的DNA微阵列，研究了钝性胸部创伤诱导的肺组织基因表达模式的时间序列。结果表明，一个高度复杂的转录程序的激活，以响应胸部创伤。胸部创伤导致炎症和凝血蛋白（如TNFα受体、IL-1α、IL-1β、C3、NF-κB和纤溶酶原激活物）表达水平升高。然而，蛋白质的上调被发现，通常不一致的发挥作用，在钝性胸部创伤（pendrin，alcohol，金属硫蛋白和糖皮质激素诱导的亮氨酸拉链）。此外，早在创伤后10分钟就观察到细胞因子和补体因子（LCR-1，C4）以及细胞内信号分子（抑制性蛋白磷酸酶）和离子通道（电压依赖性Ca 2+通道）的显著下调。总之，提供的钝性胸部创伤后炎症反应的全球视角可以为创伤病理生理学的未来研究提供一个分子框架。
After severe blunt chest trauma, the development of an acute lung injury (ALI) is often associated with severe or even lethal complications. Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute respiratory distress syndrome (ARDS)] is frequent. However, in the initial posttraumatic phase, inflammatory clinical signs are often not apparent and underlying changes in gene-expression profile are unknown. Therefore, inflammation in lung tissue following blunt chest trauma was characterized in a well-defined bilateral lung injury model. Using DNA microarrays representing 9240 genes, the temporal sequence of blunt chest trauma-induced gene-expression patterns in lung tissue was examined. The results suggest an activation of a highly complex transcriptional program in response to chest trauma. Chest trauma led to elevated expression levels of inflammatory and coagulatory proteins (such as TNFα receptor, IL-1α, IL-1β, C3, NF-κB and plasminogen activator). However, upregulation of proteins was found, usually incoherent of exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and glucocorticoid-induced leucine zipper). Furthermore, significant downregulation was observed as early as 10 min after trauma for cytokines and complement factors (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein phosphatase) and ion-channels (voltage-dependent Ca2+ channel). Taken together, the provided global perspective of the inflammatory response following blunt chest trauma could provide a molecular framework for future research in trauma pathophysiology.