Tanaka M, McCarron R M
Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892.
J Neuroimmunol. 1990 May;27(2-3):209-15. doi: 10.1016/0165-5728(90)90071-t.
The effect of both tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1) on interferon-gamma (IFN)-induced Ia expression was studied using cultured endothelial cells (EC) isolated from cerebral microvessels of SJL mice. TNF inhibited Ia induction by IFN in a dose-dependent manner. The degree of inhibition by TNF was related to the IFN concentration: 200 U/ml TNF inhibited Ia expression induced by 20 U/ml IFN by 80% and Ia induced by 100 U/ml IFN by 45%. FACS analysis revealed the induction of Ia antigen on 30-40% of EC after 3 days' culture with IFN; TNF significantly reduced the percent of EC expressing Ia antigens. Identical treatment of SJL astrocytes showed TNF augmented Ia expression induced by IFN. IL-1 also inhibited Ia induction by IFN in a manner similar to that observed with TNF. The percent reduction of Ia-positive EC by Il-1 (2.0 U/ml) was 30% and 50% during incubations with 100 and 20 U/ml IFN, respectively. When combined at suboptimal concentrations IL-1 and TNF synergistically inhibited Ia expression induced by IFN. These results demonstrate that TNF acts on EC and astrocytes in a disparate manner and indicate that TNF and IL-1 can synergistically down-regulate immune responses involving central nervous system EC.
利用从SJL小鼠脑微血管分离出的培养内皮细胞（EC），研究了肿瘤坏死因子-α（TNF）和白细胞介素-1（IL-1）对干扰素-γ（IFN）诱导的Ia表达的影响。TNF以剂量依赖的方式抑制IFN诱导的Ia表达。TNF的抑制程度与IFN浓度有关：200 U/ml TNF抑制20 U/ml IFN诱导的Ia表达达80%，抑制100 U/ml IFN诱导的Ia表达达45%。流式细胞术分析显示，用IFN培养3天后，30%-40%的EC诱导出Ia抗原；TNF显著降低了表达Ia抗原的EC百分比。对SJL星形胶质细胞进行相同处理显示，TNF增强了IFN诱导的Ia表达。IL-1也以与TNF类似的方式抑制IFN诱导的Ia表达。在分别与100 U/ml和20 U/ml IFN孵育期间，2.0 U/ml的IL-1使Ia阳性EC减少的百分比分别为30%和50%。当以次优浓度联合使用时，IL-1和TNF协同抑制IFN诱导的Ia表达。这些结果表明，TNF以不同方式作用于EC和星形胶质细胞，并表明TNF和IL-1可协同下调涉及中枢神经系统EC的免疫反应。
