Transforming growth factor β1, the dominant cytokine in murine prion disease:: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix
Transforming growth factor β1, the dominant cytokine in murine prion disease:: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix
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DOI：
10.1046/j.1365-2990.2002.00383.x
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发表时间：
2002-04-01
影响因子：
5
通讯作者：
Perry, VH
中科院分区：
文献类型：
--
作者：
Cunningham, C;Boche, D;Perry, VH
我们实验室以前的研究表明，ME7小鼠瘙痒病模型伴随着非典型炎症反应，其特征是显著的星形胶质细胞和小胶质细胞激活，但也缺乏致炎细胞因子IL-1β和IL-6的显著表达。这项研究的目的是确定在没有IL-1β和IL-6的情况下，肿瘤坏死因子(TNF)-α是否可能起到同等的促炎作用，或者是否抗炎细胞因子起主导作用。采用竞争性聚合酶链式反应和酶联免疫吸附试验检测ME7模型大鼠血清中肿瘤坏死因子-α、白介素10和转化生长因子-β1的水平。以其在脂多糖(LPS)诱导的急性炎症中的表达作为阳性对照。在急性炎症期间，所有三种细胞因子的mRNA水平都升高。而单独注射ME7的大鼠脑组织中单独的转化生长因子-β1基因表达显著升高。同样，通过酶联免疫吸附试验，我们检测到在注射内毒素的动物中IL-10、肿瘤坏死因子-α和转化生长因子-β1升高，而在注射ME7的动物中只有转化生长因子-β1显著升高。还观察到血管周围层粘连蛋白和IV型胶原沉积的增加，这与活性的转化生长因子-β1上调是一致的。这些发现表明，转化生长因子-β1可能在维持非典型小胶质细胞表型方面发挥核心作用，也可能参与血管和细胞外基质的改变。
Previous studies froth our laboratory have shown the ME7 model of murine scrapie to be accompanied by an atypical inflammatory response that is characterized by marked astroglial and microglial activation but also by the lack of significant expression of the pro-inflammatory cytokines interleukin (IL)-1beta and IL-6. The aim of this study was to determine whether, in the absence of IL-1beta and IL-6, tumour necrosis factor (TNF)-alpha may play an equivalent pro-inflammatory role, or if an anti-inflammatory cytokine profile dominates. We have used competitive polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) to determine the levels of TNF-alpha, IL-10 and transforming growth factor (TGF)-beta1 in the ME7 model. using their expression in lipopolysaccharide (LPS)-induced acute inflammation as a positive control. Levels of mRNA were elevated for all three cytokines during acute inflammation. while TGF-beta1 mRNA alone was significantly elevated in ME7-injected brains. Similarly, by ELISA, we detected elevated IL-10, TNF-alpha and TGF-beta1 in LPS-injected animals but only significant elevation of TGF-beta1 in ME7-injected animals. An increase in laminin and collagen IV deposition around blood vessels was also observed and is consistent with up-regulation by active TGF-beta1. These findings suggest that TGF-beta1 may play a central role in maintenance of an atypical microglial phenotype and may also be involved in vascular and extracellular matrix changes.