Biomedical Sciences Program, College of Health Sciences, Midwestern University, Downers Grove, IL 60515, USA.
Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA.
Toxins (Basel). 2018 Mar 21;10(4):130. doi: 10.3390/toxins10040130.
Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus () produces several toxins, but to our knowledge the bioactivity of genus LPS has not been investigated. We recently reported that cyanobacterium sp. LPS elicited classical and alternative activation of rat microglia in vitro. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria or LPS might stimulate classical and alternative activation with concomitant release of superoxide anion (O₂), matrix metalloproteinase-9 (MMP-9), cytokines and chemokines. Microglia were isolated from neonatal rats and treated in vitro with either LPS, LPS, or LPS (positive control), in a concentration-dependent manner, for 18 h at 35.9 °C. We observed that treatment of microglia with either LPS, or LPS generated statistically significant and concentration-dependent O₂, MMP-9 and pro-inflammatory cytokines IL-6 and TNF-α, pro-inflammatory chemokines MIP-2/CXCL-2, CINC-1/CXCL-1 and MIP-1α/CCL3, and the anti-inflammatory cytokine IL-10. Thus, our results provide experimental support for our working hypothesis because both and LPS elicited classical and alternative activation of microglia and concomitant release of O₂, MMP-9, cytokines and chemokines in a concentration-dependent manner in vitro. To our knowledge this is the first report on the toxicity of cyanobacteria and LPS to microglia, an immune cell type involved in neuroinflammation and neurotoxicity in the central nervous system.
泛生革兰氏阴性蓝藻通过在陆地、海洋和淡水中产生的毒素(如脂多糖 (LPS))污染环境,可能会影响人类和动物的健康。蓝藻属 () 产生多种毒素,但据我们所知,属 LPS 的生物活性尚未得到研究。我们最近报道称,蓝藻 sp. LPS 在体外引发大鼠小胶质细胞的经典和替代激活。因此,我们假设体外用蓝藻 或 LPS 处理脑小胶质细胞可能会刺激经典和替代激活,同时释放超氧阴离子 (O₂)、基质金属蛋白酶-9 (MMP-9)、细胞因子和趋化因子。小胶质细胞从小鼠新生儿中分离出来,并在 35.9°C 下以浓度依赖性方式用 LPS、 LPS 或 LPS(阳性对照)体外处理 18 小时。我们观察到,用 LPS、 或 LPS 处理小胶质细胞会产生统计学上显著的、浓度依赖性的 O₂、MMP-9 和促炎细胞因子 IL-6 和 TNF-α、促炎趋化因子 MIP-2/CXCL-2、CINC-1/CXCL-1 和 MIP-1α/CCL3 以及抗炎细胞因子 IL-10。因此,我们的结果为我们的工作假设提供了实验支持,因为 LPS 和 LPS 都在体外以浓度依赖性方式引发小胶质细胞的经典和替代激活,并伴随 O₂、MMP-9、细胞因子和趋化因子的释放。据我们所知,这是关于蓝藻 和 LPS 对小胶质细胞(一种参与中枢神经系统神经炎症和神经毒性的免疫细胞类型)毒性的首次报道。