Hamano Hiroko, Noguchi Masashi, Fukui Hidekimi, Issiki Atsushi, Watanabe Yasuo
Department of Anesthesiology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, 160-0023, Tokyo, Japan.
Life Sci. 2002 Dec 20;72(4-5):565-74. doi: 10.1016/s0024-3205(02)02252-x.
Bacterial endotoxin lipopolysaccharide (LPS) treatment of neuron-rich cells and glia-rich cells exhibited significant cell damage 12 hr after incubation, although no severe or significant cell damage induced by LPS appeared in neuron-glia co-cultured cells. Moreover, severe and significant time-dependent cell damage was induced by a larger dose treatment (10 mM) of glutamate (Glu), and this damage was seen in neuron-rich cells, neuron-glia co-cultured cells, and glia-rich cells. Examining extracellular tumor necrosis factor alpha (TNFalpha) induced by either LPS or Glu treatment, the levels of extracellular TNFalpha induced by LPS were significantly higher than those induced by Glu. These significant increases of TNFalpha were measured within 2 hr after LPS treatment in neuron-glia co-cultured cells and glia-rich cells, although no significant changes were detected in the neuron-rich cells. With Glu treatment, a significant increase in TNFalpha levels was detected after 6 hr of Glu treatment only in glia-rich cells. Our results indicate that cerebral TNFalpha is mainly produced in glia cells and that its production is dependently regulated by each stimulant. In addition, the production of TNFalpha is not directly related to the trigger of cell injury.
用细菌内毒素脂多糖（LPS）处理富含神经元的细胞和富含神经胶质的细胞，孵育12小时后出现明显的细胞损伤，尽管在神经元-神经胶质共培养细胞中未出现由LPS诱导的严重或明显的细胞损伤。此外，较大剂量（10 mM）的谷氨酸（Glu）处理会诱导严重且明显的时间依赖性细胞损伤，这种损伤在富含神经元的细胞、神经元-神经胶质共培养细胞和富含神经胶质的细胞中均可见。检测LPS或Glu处理诱导的细胞外肿瘤坏死因子α（TNFα），LPS诱导的细胞外TNFα水平显著高于Glu诱导的水平。在神经元-神经胶质共培养细胞和富含神经胶质的细胞中，LPS处理后2小时内检测到TNFα的这些显著升高，尽管在富含神经元的细胞中未检测到显著变化。用Glu处理时，仅在富含神经胶质的细胞中，Glu处理6小时后检测到TNFα水平显著升高。我们的结果表明，脑内TNFα主要在神经胶质细胞中产生，其产生受每种刺激物的依赖性调节。此外，TNFα的产生与细胞损伤的触发没有直接关系。
