摘要
目的从免疫细胞表面模式识别受体水平揭示创伤感染条件下炎症反应的发生机制,为探寻有效调控炎症反应的措施提供新思路。方法选择小鼠内毒素血症、盲肠结扎穿孔、肺泡巨噬细胞免疫刺激模型,以免疫组织化学法和RT-PCR法检测主要模式识别受体的表达;利用细胞转染模型研究CD14、TLR4、MD-2相互作用及其与跨膜信号转导的关系。结果免疫细胞清道夫受体和CD14、TLR4、MD-2,分别呈现下调和上调表达,且转染CD14、TLR4和MD-23种表达质粒的HEK293细胞株对FITC-LPS结合率最强(P<0.05),在内毒素刺激后NF-κB活性、TNF-α分泌最显著(P<0.05)。结论免疫细胞表面防御性受体下调和效应性受体上调参与炎症反应失控过程,调控模式识别受体表达对减轻机体炎性损伤有重要意义。
Objective To investigate the possible mechanisms of traumatic infection-related inflammation via the pattern recognition receptors （PRRs） in innate immunocytes and provide the new idea for the measures in modulation of the excessive inflammatory responses. Methods The models of endotoxemic mice, cecal liga- tion and puncture, and immmunostimulated alveolar macrophages were used for the assay of PRRs by immunohistochemistry and reverse transcription PCR method. HEK293 cells co-transfected plasmids expressing CDI4, TLR4 and MD-2 or two of them were stimulated with lipopolysaccharide （LPS） at the dose of 100 ng/ml for the determination of NF-κB and tumor necrosis factor （TNF）-α. Results SR was up-regulated while the expressions of CD14, TLR4 and MD-2 were down-regulated in innate immunocytes. The HEK293 cells co-transfected three types of plasmids enhanced the sensitivity to LPS binding and stimulation as compared with HEK293 cells co-transfected two of them （ P 〈 0.05 ） , followed with the significant translocation of NF-κB and TNF-α secretion （P 〈 0.05 ）. Conclusion Our data strongly indicate that the significant correlation between uncontrolled inflammatory responses and the imbalance between defensive receptors and effector receptors. The strategy of moderate regulation of PRRs can be a promising strategy in immunomodulation of inflammatory injuries.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2009年第15期1421-1424,共4页
Journal of Third Military Medical University
基金
国家重点基础研究发展计划(973计划)(2005CB522602,1999054203)
全军医学科研“十一五”计划科技攻关项目(06G080)~~
关键词
模式识别受体
内毒素
创伤和损伤
pattern recognition receptors
endotoxin, innate immune
trauma and injury
