Substance P in Polymicrobial Sepsis: Molecular Fingerprint of Lung Injury in Preprotachykinin-A-/- Mice
Substance P in Polymicrobial Sepsis: Molecular Fingerprint of Lung Injury in Preprotachykinin-A-/- Mice
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DOI：
10.2119/molmed.2009.00166
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发表时间：
2010-05-01
影响因子：
5.7
通讯作者：
Bhatia, Madhav
中科院分区：
文献类型：
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作者：
Hegde, Akhil;Tamizhselvi, Ramasamy;Bhatia, Madhav
缺失主要编码神经肽P物质的小鼠原纤裂素- a （PPTA）已被证明可以预防败血症的肺损伤和死亡率。本研究探讨了微生物脓毒症诱导8 h后小鼠肺组织中基于微阵列的差异基因表达谱以及PPTA基因缺失的影响。在微阵列分析中评估了一系列基因差异表达（超过两倍），将野生型和敲除ppta的脓毒症小鼠与各自的假对照组进行了比较，并进一步验证了数据。P物质基因缺失导致脓毒症诱导后炎症和免疫调节相关基因的表达谱与野生型小鼠相比有显著差异。有趣的是，除了各种促炎介质外，抗炎细胞因子白细胞介素-1受体拮抗剂基因（ILTRN）在PPTA（-/-）脓毒症小鼠中也升高得更多。此外，半定量RT-PCR分析支持微阵列数据。微阵列数据表明，ppta敲除小鼠脓毒症早期炎症基因表达水平升高可能是为了在不过度抑制免疫的情况下解决感染。由于科学家对促炎介质和抗炎介质在败血症中的作用存在分歧，因此根据完整的基因组图谱来定义状态似乎是谨慎的。这是第一篇利用微阵列分析研究盲肠结扎和穿刺性败血症的ppta基因敲除小鼠肺基因表达谱的报告，并为肺损伤和死亡率的保护提供了额外的生物学见解。(C) 2010年，范斯坦医学研究所，www.feinsteininstitute.org
Deletion of mouse preprotachykinin-A (PPTA), which encodes mainly for neuropeptide substance P has been shown to protect against lung injury and mortality in sepsis. This study explored microarray-based differential gene expression profiles in mouse lung tissue 8 h after inducing microbial sepsis and the effect of PPTA gene deletion. A range of genes differentially expressed (more than two-fold) in microarray analysis was assessed, comparing wild-type and PPTA-knockout septic mice with their respective sham controls, and the data were further validated. Genetic deletion of substance P resulted in a significantly different expression profile of genes involved in inflammation and immunomodulation after the induction of sepsis, compared with wild-type mice. Interestingly, apart from the various proinflammatory mediators, the antiinflammatory cytokine interleukin-1 receptor antagonist gene (ILTRN) was also elevated much more in PPTA(-/-) septic mice. In addition, semiquantitative RT-PCR analysis supported the microarray data. The microarray data imply that the elevated levels of inflammatory gene expression in the early stages of sepsis in PPTA-knockout mice are possibly aimed to resolve the infection without excessive immunosuppression. As scientists are divided over the effects of pro- and antiinflammatory mediators in sepsis, it seems prudent to define the status depending on a complete genome profile. This is the first report exploring pulmonary gene expression profiles using microarray analysis in PPTA-knockout mice subjected to cecal ligation and puncture-induced sepsis and providing additional biological insight into the protection received against lung injury and mortality. (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.org