Lipopolysaccharide induces preprotachykinin gene expression
Lipopolysaccharide induces preprotachykinin gene expression
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DOI：
10.1165/rcmb.2002-0107oc
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发表时间：
2003-11-01
影响因子：
6.4
通讯作者：
Lai, YL
中科院分区：
文献类型：
--
作者：
Huang, HY;Lai, YL
本研究通过分析速激肽前体pre - protachykinin- i （PPT-I）基因表达，来验证速激肽的生物合成是否在脂多糖（LPS）诱导的气道改变中起关键作用。褐威大鼠（11-12周龄）分为4组：对照组；嘴唇;二甲基硫脲（DMTU，一种有效的羟基自由基清除剂）；DMTU + LPS。对照组给予生理盐水处理。LPS组的49只动物被进一步分为7个亚组，以测试LPS治疗的剂量和时间的影响。采用实时定量逆转录-聚合酶链反应，提取结节神经节和肺总RNA，测定PPT-I mRNA的相对含量。此外，测定lps诱导气道对支气管收缩剂的反应、中性内肽酶（NEP）基因表达、白细胞计数、SP和降钙素基因相关肽（CGRP）水平的改变。LPS （4 mg/kg，腹腔）在4 h后显著提高结节神经节和12 h后肺组织中PPT-I mRNA水平，并持续5 d。LPS显著增加NEP mRNA、SP和CGRP水平，气道对辣椒素和SP的反应性以及中性粒细胞计数，但显著降低巨噬细胞计数。我们的数据支持lps诱导的支气管对辣椒素的高反应性与速激肽基因表达的上调密切相关，而与NEP的上调无关。
This study was performed to test whether biosynthesis of tachykinins plays a pivotal role in lipopolysaccharide (LPS)induced airway alteration by analyzing preprotachykinin-I (PPT-I, a precursor of tachykinins) gene expression. Brown-Norway rats (11-12 wk old) were divided into four groups: control; LIPS; dimethylthiourea (DMTU, an effective hydroxyl radical scavenger); and DMTU + LPS. Each animal in the control group received saline treatment. Forty-nine animals in the LIDS group were further divided into seven subgroups to test effects of doses and length of the LPS treatment. Total RNA extracted from nodose ganglia and lungs was used to assay relative amount of PPT-I mRNA using the real-time quantitative reverse transcriptase-polymerase chain reaction. In addition, LPS-induced alterations in airway responses to bronchial constrictors, neutral endopeptidase (NEP) gene expression, leukocyte counts, and SP and calcitonin gene-related peptide (CGRP) levels were determined. LPS (4 mg/kg, intraperitoneal) raised significantly PPT-I mRNA level after 4 h in nodose ganglia and 12 h in the lung, and this elevation sustained for 5 d. Also, LPS caused significant increases in NEP mRNA, SP and CGRP levels, airway reactivity to capsaicin and SP, and neutrophil counts, but a significant decrease in macrophage count. Our data support that LPS-induced bronchial hyperreactivity to capsaicin is related closely to the upregulation of tachykinin gene expression, but not the upregulation of NEP.