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Chitosan Oligosaccharides Inhibit the Expression of Interleukin‐6 in Lipopolysaccharide‐induced Human Umbilical Vein Endothelial Cells Through p38 and ERK1/2 Protein Kinases
Author(s) -
Liu HongTao,
Li WenMing,
Li XiuYing,
Xu QingSong,
Liu QiShun,
Bai XueFang,
Yu Chao,
Du YuGuang
Publication year - 2010
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2009.00493.x
Subject(s) - umbilical vein , p38 mitogen activated protein kinases , mapk/erk pathway , lipopolysaccharide , kinase , protein kinase a , signal transduction , mitogen activated protein kinase , phosphorylation , microbiology and biotechnology , chemistry , nf κb , pharmacology , biology , biochemistry , immunology , in vitro
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 μg/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 μg/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 κB (NF‐κB). Moreover, the LPS‐induced NF‐κB activation was suppressed by the specific ERK1/2 inhibitor PD98059 (30 μM) ( versus the LPS‐treated group, p < 0.01), but not by the specific p38 MAPK inhibitor SB203580 (25 μM). 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‐κB activation and one via ERK1/2 pathway dependent on NF‐κB activation.