Hu S, Sheng W S, Peterson P K, Chao C C
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
Glia. 1995 Jan;13(1):45-50. doi: 10.1002/glia.440130106.
Activated microglia may contribute to two opposite effects during inflammation within the central nervous system: host defense against microorganisms and neuronal injury. Each of these processes may be mediated by the generation of reactive oxygen intermediates by activated microglia. We investigated the effects of two proinflammatory cytokines, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, and of the anti-inflammatory cytokine, transforming growth factor (TGF)-beta, on murine microglial cell superoxide (O2-) production upon stimulation with phorbol myristate acetate (PMA). Priming of microglia with IFN-gamma or TNF-alpha resulted in a dose-dependent enhancement of O2- release in response to PMA. The priming effects of these two cytokines were additive, suggesting that they acted by independent mechanisms. We also found that IFN-gamma and TNF-alpha stimulated the release of bioactive TGF-beta and that treatment of microglial cell cultures with TGF-beta antagonized the priming effects of IFN-gamma and TNF-alpha on O2- production. The results of this study have implications for understanding the mechanisms by which cytokines and microglia may contribute to host defense as well as to injury of the brain.
在中枢神经系统炎症过程中，活化的小胶质细胞可能产生两种相反的作用：抵御微生物的宿主防御和神经元损伤。这些过程中的每一个都可能由活化的小胶质细胞产生活性氧中间体介导。我们研究了两种促炎细胞因子，即干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α，以及抗炎细胞因子转化生长因子（TGF）-β，对佛波酯（PMA）刺激后小鼠小胶质细胞超氧化物（O2-）产生的影响。用IFN-γ或TNF-α预处理小胶质细胞会导致对PMA反应的O2-释放呈剂量依赖性增强。这两种细胞因子的预处理作用是相加的，表明它们通过独立的机制起作用。我们还发现IFN-γ和TNF-α刺激了生物活性TGF-β的释放，并且用TGF-β处理小胶质细胞培养物可拮抗IFN-γ和TNF-α对O2-产生的预处理作用。本研究结果对于理解细胞因子和小胶质细胞可能有助于宿主防御以及脑损伤的机制具有重要意义。
