Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: An in situ hybridization study
Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: An in situ hybridization study
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DOI：
10.1111/j.1460-9568.1997.tb01497.x
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发表时间：
1997-07-01
影响因子：
3.4
通讯作者：
Schwab, ME
中科院分区：
文献类型：
--
作者：
Bartholdi, D;Schwab, ME
脊髓损伤在局部病变区域诱发复杂的细胞级联反应：继发性细胞死亡和炎症反应以及瘢痕和空洞形成发生。为了研究这种局部损伤反应的分子特征并确定其病理生理意义，我们研究了促炎和趋化因子在实验性小鼠脊髓损伤模型中的表达模式。我们通过原位杂交显示，促炎细胞因子TNF α和il -1以及趋化因子MIP-1 α和MIP-1 β的转录本在损伤后的第一个小时内上调。在这个早期阶段，促炎细胞因子的表达仅限于病变区域周围的细胞，可能是常驻中枢神经系统细胞。虽然TNF α在一个非常狭窄的时间窗口内表达，但IL-1可以在第二阶段的多形核粒细胞亚群中被检测到，这些粒细胞大约在6小时左右迁移到脊髓。趋化因子MIP-1 α和β的信息在24小时左右在整个脊髓的灰质中以一种普遍的方式表达，并在损伤后4天再次被限制在病变部位的细胞浸润。有趣的是，我们的数据表明，常驻中枢神经系统细胞，最有可能是小胶质细胞，而不是外周炎症细胞，是细胞因子和趋化因子mrna的主要来源。观察到的明确的细胞因子模式表明，中枢神经系统损伤后的炎症事件受到严格控制。促炎细胞因子和趋化因子信息的早期表达可能是炎症细胞募集的重要因素。观察到的特定细胞因子模式的其他病理生理后果仍有待确定。
Injury to the spinal cord induces a complex cascade of cellular reactions at the local lesion area: secondary cell death and inflammatory reactions as well as scar and cavity formation take place. In order to investigate the molecular features underlying this local wounding response and to determine their pathophysiological implications, we studied the expression pattern of pro-inflammatory and chemoattractant cytokines in an experimental spinal cord injury model in mouse. We show by in situ hybridization that transcripts for the pro-inflammatory cytokines TNF alpha and IL-l as well as the chemokines MIP-1 alpha and MIP-1 beta are upregulated within the first hour following injury. In this early phase, the expression of the pro-inflammatory cytokines is restricted to cells in the surroundings of the lesion area probably resident CNS cells. While TNF alpha is expressed in a very narrow time window, IL-1 can be detected in a second phase in a subset of polymorphonuclear granulocytes which immigrate into the spinal cord around 6 h. Message for the chemokines MIP-1 alpha and beta is expressed in a generalized way in the grey matter of the entire spinal cord around 24 h and gets again restricted to the cellular infiltrate at the lesion site at 4 days following injury. Interestingly, our data suggest that resident CNS cells, most probably microglial cells, and not peripheral inflammatory cells, are the main source for cytokine and chemokine mRNAs. The defined cytokine pattern observed indicates that the inflammatory events upon lesioning the CNS are tightly controlled. The very early expression of pro-inflammatory cytokine and chemokine messages may represent an important element of the recruitment of inflammatory cells. Additional pathophysiological consequences of the specific cytokine pattern observed remain to be determined.