Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, Illinois 60515, USA.
Mar Drugs. 2007;5(3):113-35. doi: 10.3390/md503113.
The excitatory amino acid domoic acid is the causative agent of amnesic shellfish poisoning in humans. The in vitro effects of domoic acid on rat neonatal brain microglia were compared with E. coli lipopolysaccharide (LPS), a known activator of microglia mediator release over a 4 to 24 hour observation period. LPS [3 ng/mL] but not domoic acid [1 mM] stimulated a statistically significant increase in TNF-alpha mRNA and protein generation. Furthermore, both LPS and domoic acid did not significantly affect TGF-beta1 gene expression and protein release. Finally, an in vitro exposure of microglia to LPS resulted in statistically significant MMP-9 expression and release, thus extending and confirming our previous observations. However, in contrast, no statistically significant increase in MMP-9 expression and release was observed after domoic acid treatment. Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to neuronal cells, activates rat neonatal microglia and the concomitant release of the pro-inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases-9 (MMP-9), as well as the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1).
兴奋性氨基酸软骨藻酸是人类记忆缺失性贝类中毒的致病因子。在体外，将软骨藻酸对大鼠新生脑小胶质细胞的作用与大肠杆菌脂多糖（LPS）进行了比较，LPS 是一种已知的小胶质细胞介质释放的激活剂，观察时间为 4 至 24 小时。LPS（3ng/ml）但不是软骨藻酸（1mm）刺激 TNF-α mRNA 和蛋白生成的统计学显著增加。此外，LPS 和软骨藻酸均未显著影响 TGF-β1 基因表达和蛋白释放。最后，体外小胶质细胞暴露于 LPS 导致 MMP-9 的表达和释放具有统计学意义，从而扩展和证实了我们以前的观察结果。然而，与 LPS 相反，软骨藻酸处理后 MMP-9 的表达和释放没有统计学显著增加。总之，我们的观察结果不支持以下假说，即短期（4 至 24 小时）体外暴露于神经元细胞毒性浓度的软骨藻酸激活大鼠新生小胶质细胞，同时释放促炎介质肿瘤坏死因子-α（TNF-α）和基质金属蛋白酶-9（MMP-9），以及抗炎细胞因子转化生长因子-β1（TGF-β1）。
