Chitosan oligosaccharides inhibit the expression of interleukin-6 in lipopolysaccharide-induced human umbilical vein endothelial cells through p38 and ERK1/2 protein kinases.
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.
Liu
Hong-Tao
HT
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Li
Wen-Ming
WM
Li
Xiu-Ying
XY
Xu
Qing-Song
QS
Liu
Qi-Shun
QS
Bai
Xue-Fang
XF
Yu
Chao
C
Du
Yu-Guang
YG
D048271:Chitosan / Q000378:metabolism / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048053:Mitogen-Activated Protein Kinase 6 / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology; D010766:Phosphorylation; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D048271:Chitosan; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6; D048051:p38 Mitogen-Activated Protein Kinases