Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.
Inflamm Res. 2011 Feb;60(2):175-85. doi: 10.1007/s00011-010-0252-y. Epub 2010 Sep 24.
This study aimed to characterize postnatal development of lipopolysaccharide (LPS)-induced inflammatory response in the brain.
Postnatal day (P)1, P21 and P70 Sprague-Dawley(®) rats were treated with saline or 0.25 mg/kg LPS for 2 h, and the mRNA expression of neuroinflammatory mediators in the brain was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). The kinetics of LPS-induced neuroinflammatory mediators in the brain of P1 and P21 animals was determined using RT-PCR, and the kinetics of LPS-induced cytokines in the serum were determined using ELISA. The basal levels of Toll-like receptor (TLR)-4, CD14, and myeloid differentiation factor 88 (Myd88) were measured at the mRNA and protein levels using RT-PCR and Western blot assay respectively.
The mRNA expression levels of cytokines and chemokines were considerably increased in P21 and P70 brains but not significantly altered in P1 brain at 2 h following LPS stimulation. Instead, the induction of cytokines and chemokines was significantly delayed in the brain of P1 animals following LPS stimulation, which was associated with diminished Myd88 production in P1 brain. In parallel, the cytokine response in the serum of P1 animals after LPS stimulation was also delayed compared to P21 animals.
TLR-4-mediated innate immunity in the brain was significantly delayed in P1 animals, and underwent significant development during the early postnatal period.
本研究旨在描述脂多糖（LPS）诱导的大脑炎症反应的产后发育特征。
对 P1、P21 和 P70 斯普拉格-道利（®）大鼠进行生理盐水或 0.25mg/kg LPS 处理 2 小时，采用逆转录-聚合酶链反应（RT-PCR）检测大脑中神经炎症介质的 mRNA 表达。采用 RT-PCR 测定 P1 和 P21 动物脑中 LPS 诱导的神经炎症介质的动力学，采用 ELISA 测定血清中 LPS 诱导的细胞因子的动力学。采用 RT-PCR 和 Western blot 分析分别测定 TLR-4、CD14 和髓样分化因子 88（Myd88）在 mRNA 和蛋白水平上的基础水平。
LPS 刺激后 2 小时，P21 和 P70 脑中细胞因子和趋化因子的 mRNA 表达水平显著增加，但 P1 脑内无明显变化。相反，LPS 刺激后 P1 动物脑中细胞因子和趋化因子的诱导明显延迟，这与 P1 脑中 Myd88 产生减少有关。平行地，与 P21 动物相比，LPS 刺激后 P1 动物血清中的细胞因子反应也延迟。
P1 动物的 TLR-4 介导的大脑先天免疫明显延迟，并在出生后早期阶段经历了显著的发育。
