Peripheral injection of lipopolysaccharide enhances expression of inflammatory cytokines in murine locus coeruleus: possible role of increased norepinephrine turnover
Peripheral injection of lipopolysaccharide enhances expression of inflammatory cytokines in murine locus coeruleus: possible role of increased norepinephrine turnover
复制标题
DOI：
10.1111/j.1471-4159.2005.03209.x
复制
发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Ota, A
中科院分区：
文献类型：
--
作者：
Kaneko, YS;Mori, K;Ota, A
已知细胞因子和儿茶酚胺构成参与维持中枢神经系统（CNS）内稳态的调节性神经免疫网络的重要部分。虽然我们已经报道了在腹膜内（i. p.）注射脂多糖（LPS），这种增加的含义仍然不清楚。鉴于去甲肾上腺素（NE）通过负调节促炎细胞因子表达以抗炎方式起作用的证据，我们检查了腹腔注射LPS后C3 H/HeN小鼠（雄性，8周龄）LC中的炎性细胞因子表达水平。LC内IL-1 β和TNF-α基因的mRNA表达水平在LPS注射后的前2 h内增加，并在4 h和15 h出现两个高峰。小胶质细胞，这是在中枢神经系统中产生促炎细胞因子的主要细胞类型之一，从小鼠新生儿脑中分离，以更精确地阐明NE含量的变化和LC中炎性细胞因子的上调之间的关系。同时孵育的小胶质细胞与LPS和NE增强IL-1 β在mRNA和蛋白水平的表达，但降低TNF-α的mRNA和蛋白水平。这些数据支持NE负调节促炎细胞因子表达的假设，至少在TNF-α的情况下，其作用可能有助于观察到的NE的抗炎性质。这份报告，在体内和体外实验的结果的基础上，是第一个建议NE含量和细胞因子的表达水平在中枢神经系统之间的关系。
Cytokines and catecholamines are known to constitute a significant portion of the regulatory neuroimmune networks involved in maintaining homeostasis in the central nervous system (CNS). Although we have already reported an increase in norepinephrine (NE) turnover within the locus coeruleus (LC) at 2 and 4 h after the intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), the implication of this increase remains unclear. In view of evidence that norepinephrine (NE) acts in an anti-inflammatory manner by way of negatively regulating pro-inflammatory cytokine expression, we examined the inflammatory cytokine expression levels in the LC of C3H/HeN mice (male, 8 weeks old) after an i.p. LPS injection. The mRNA expression levels of the genes encoding IL-1 beta and TNF-alpha within the LC increased during the first 2 h, and showed two peaks, the first at 4 h and the second lesser one at 15 h after the LPS injection. Microglia, which are one of the major cell types that produce pro-inflammatory cytokines in the CNS, were isolated from mouse neonate brains in order to clarify more precisely the relationship between the changes in NE content and the up-regulation of inflammatory cytokines in the LC. Simultaneous incubation of microglia with LPS and NE enhanced the expression of IL-1 beta at both mRNA and protein levels, but reduced the mRNA and protein levels of TNF-alpha. These data support the hypothesis that NE negatively regulates the expression of pro-inflammatory cytokine expression, at least in the case of TNF-alpha, which action could contribute to the observed anti-inflammatory properties of NE. This report, based on the results of both in vivo and in vitro experiments, is the first to suggest a relationship between NE content and cytokine expression levels in the CNS.