Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Basic Clin Pharmacol Toxicol. 2010 May;106(5):362-71. doi: 10.1111/j.1742-7843.2009.00493.x. Epub 2009 Nov 17.
Chitosan oligosaccharides (COS) have been reported to exert anti-fungal activities, antitumour activities and immuno-enhancing effects. However, the potential roles of COS in the treatment of vascular inflammations remain unknown. In the present study, we examined the effects of COS on interleukin-6 (IL-6) production in human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS). Induction of HUVECs with LPS (100 ng/ml) increased the mRNA expression and protein secretion of IL-6 (versus the vehicle-treated group, p < 0.01), which were significantly reverted by the pre-treatment with COS (50-200 microg/ml) for 24 hr before LPS exposure (versus the LPS-treated group, p < 0.05 or 0.01). Signal transduction studies showed that the pre-treatment of HUVECs with COS (50-200 microg/ml) for 24 hr markedly inhibited the LPS-induced over-expression of phosphorylated p38 mitogen-activated protein kinase (MAPK), phosphorylated ERK1/2 and nuclear factor kappaB (NF-kappaB). Moreover, the LPS-induced NF-kappaB activation was suppressed by the specific ERK1/2 inhibitor PD98059 (30 microM) (versus the LPS-treated group, p < 0.01), but not by the specific p38 MAPK inhibitor SB203580 (25 microM). Additionally, both MAPK inhibitors markedly suppressed LPS-induced IL-6 mRNA expression in HUVECs (versus the LPS-treated group, p < 0.01). In conclusion, our results suggest that COS inhibit LPS-induced up-regulation of IL-6 in HUVECs, and this can be regulated by at least two parallel signalling pathways: one via p38 MAPK pathway independent of NF-kappaB activation and one via ERK1/2 pathway dependent on NF-kappaB activation.
壳寡糖（COS）已被报道具有抗真菌、抗肿瘤和免疫增强作用。然而，COS 在治疗血管炎症中的潜在作用尚不清楚。在本研究中，我们研究了 COS 对脂多糖（LPS）诱导的人脐静脉内皮细胞（HUVEC）中白细胞介素-6（IL-6）产生的影响。用 LPS（100ng/ml）诱导 HUVEC 增加了 IL-6 的 mRNA 表达和蛋白分泌（与对照组相比，p < 0.01），而在 LPS 暴露前用 COS（50-200μg/ml）预处理 24 小时则显著逆转了这一作用（与 LPS 处理组相比，p < 0.05 或 0.01）。信号转导研究表明，COS（50-200μg/ml）预处理 HUVEC 24 小时可显著抑制 LPS 诱导的磷酸化 p38 丝裂原活化蛋白激酶（MAPK）、磷酸化 ERK1/2 和核因子κB（NF-κB）的过度表达。此外，LPS 诱导的 NF-κB 激活被特异性 ERK1/2 抑制剂 PD98059（30μM）抑制（与 LPS 处理组相比，p < 0.01），但不被特异性 p38 MAPK 抑制剂 SB203580（25μM）抑制。此外，两种 MAPK 抑制剂均显著抑制 LPS 诱导的 HUVEC 中 IL-6 mRNA 表达（与 LPS 处理组相比，p < 0.01）。总之，我们的结果表明，COS 抑制 LPS 诱导的 HUVEC 中 IL-6 的上调，这可以通过至少两种平行的信号通路来调节：一种是通过 p38 MAPK 通路，不依赖于 NF-κB 激活，另一种是通过 ERK1/2 通路，依赖于 NF-κB 激活。
