D'Souza S D, Antel J P, Freedman M S
Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Quebec, Canada.
J Neuroimmunol. 1994 Feb;50(1):17-24. doi: 10.1016/0165-5728(94)90210-0.
In this study, we examined the role of cytokines, known to be in elevated levels in multiple sclerosis (MS) plaques, in regulating oligodendrocyte (ODC) expression of heat shock protein (hsp) in human brain-derived glial cell cultures. Using dual-stain immunohistochemistry, we initially compared the ability of a mixture of cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, TNF-alpha, TNF-beta, IFN-beta and IFN-gamma) with that of physical stimuli such as heat shock and peroxide, to increase cellular expression of the mainly inducible hsp72 species in mixed glial cell cultures (containing ODC, astrocytes and microglia). Similar to heat shock and peroxide, the cytokine mixture induced hsp72 expression only in ODC (70 +/- 5% vs. a baseline of 3 +/- 1% positive cells). When used individually, however, only IL-1 alpha (79 +/- 3%), IFN-gamma (70 +/- 2%) and TNF-alpha (65 +/- 5%) induced ODC hsp72 expression in mixed glial cell cultures. In purified ODC preparations, only IL-1 alpha induced hsp72 expression (84 +/- 4%). An IL-1 receptor antagonist (IL-1ra), abrogated hsp72 induction by IL-1 alpha (16 +/- 3%) as well as that due to IFN-gamma (14 +/- 1%) and TNF-alpha (13 +/- 2%) in mixed glial cell cultures. Furthermore, ODC express IL-1 receptors, detected by confocal laser scanning microscopy. Our data indicate that cytokines mediate hsp induction in ODC possibly via a final common pathway involving IL-1 binding to its receptor on ODC. Such interaction could enhance any putative ODC-immune interactions which are dependent on hsp molecule recognition.
在本研究中，我们检测了已知在多发性硬化症（MS）斑块中水平升高的细胞因子，在调节人脑源性胶质细胞培养物中少突胶质细胞（ODC）热休克蛋白（hsp）表达方面的作用。使用双重染色免疫组织化学，我们首先比较了细胞因子混合物（IL-1α、IL-1β、IL-2、IL-6、IL-8、TNF-α、TNF-β、IFN-β和IFN-γ）与热休克和过氧化物等物理刺激在混合胶质细胞培养物（包含ODC、星形胶质细胞和小胶质细胞）中增加主要可诱导的hsp72种类细胞表达的能力。与热休克和过氧化物相似，细胞因子混合物仅在ODC中诱导hsp72表达（70±5%，而阳性细胞基线为3±1%）。然而，单独使用时，在混合胶质细胞培养物中只有IL-1α（79±3%）、IFN-γ（70±2%）和TNF-α（65±5%）诱导ODC hsp72表达。在纯化的ODC制剂中，只有IL-1α诱导hsp72表达（84±4%）。一种IL-1受体拮抗剂（IL-1ra）消除了混合胶质细胞培养物中IL-1α（16±3%）以及IFN-γ（14±1%）和TNF-α（13±2%）诱导的hsp72。此外，通过共聚焦激光扫描显微镜检测到ODC表达IL-1受体。我们的数据表明，细胞因子可能通过涉及IL-1与其在ODC上的受体结合的最终共同途径介导ODC中的hsp诱导。这种相互作用可能增强任何依赖于hsp分子识别的假定ODC-免疫相互作用。
