首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model.
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Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model.

机译:在鼠神经胶质瘤模型中,TGF beta1的局部产生可抑制脑水肿,增强TNF-α诱导的细胞凋亡,并提高生存率。

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We have previously reported that local secretion of either TNF-alpha or TGF beta1 by intracerebral SMA-560 malignant glioma tumor cells can reduce or eliminate tumor growth in mice. However, the use of TNF-alpha, while improving the overall survival of tumor bearing animals, was associated with early toxic deaths due to cerebral edema. In the present study, we demonstrate that TNF-alpha induces apoptosis of the SMA 560 cell line, as does TGF beta1, and that these two cytokines act in an additive fashion to enhance apoptosis and thus, to inhibit SMA 560 cell growth in vitro. Next, we show that the production of TGF beta1 when added to TNF-alpha production by central nervous system tumors in vivo abrogates any early deaths seen due to TNF-alpha toxicity and leads to a larger percentage of animals surviving CNS tumor challenge. Finally, we demonstrate that the production of TGF beta1 by tumor cells is associated with the abolition of tumor-associated cerebral edema in both TNF-alpha and in non-TNF-alpha producing tumors. These results are important for the development of effective and less toxic therapies for brain tumors, as well as for examining the pathogenesis of tumor-related cerebral edema.
机译:我们以前曾报道过,大脑内SMA-560恶性神经胶质瘤肿瘤细胞局部分泌TNF-α或TGF beta1可以减少或消除小鼠的肿瘤生长。但是,使用TNF-α可以改善荷瘤动物的整体存活率,但与脑水肿导致的早期毒性死亡有关。在本研究中,我们证明TNF-α与TGF beta1一样诱导SMA 560细胞系的凋亡,并且这两种细胞因子以累加方式起作用以增强凋亡,从而在体外抑制SMA 560细胞的生长。接下来,我们证明了当体内中枢神经系统肿瘤将TGF beta1的产生添加到TNF-α的产生时,它消除了由于TNF-α毒性而导致的任何早期死亡,并导致了更大比例的动物在中枢神经系统肿瘤攻击中幸存下来。最后,我们证明了肿瘤细胞产生TGFβ1与废除TNF-α和非TNF-α肿瘤中与肿瘤相关的脑水肿有关。这些结果对于开发有效且毒性较小的脑肿瘤疗法以及检查与肿瘤相关的脑水肿的发病机理具有重要意义。

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