Abstract
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Lipopolysaccharide Enhances Beta2-Glycoprotein I Activation of Nuclear Factor κB in Liver Cancer Cells
by Xue Jing, Zi-Bin Tian, Pu-Jun Gao, Nai-Jun Han, Yong-Hong Xu, Han Zhang, Xue-Li Ding, Xiao-Wei Wang, Xie Man, Cui-ping Zhang
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Background: Beta2-glycoprotein I (β2GPI) is a highly abundant glycoprotein in plasma. Our previous study demonstrated strong β2GPI expression in hepatitis B-related hepatocellular carcinoma (HCC) tissue and the combination of β2GPI and hepatitis B surface antigen (HBsAg) was shown to significantly activate the nuclear factor kappa B (NF-κB). To investigate whether lipopolysaccharide (LPS) enhances β2GPI activation of NF-κB and the expression of downstream factors (e.g., tumor necrosis factor alpha, TNF-α; interleukin-1 beta, IL-1β; alpha-fetoprotein, AFP) in the human hepatoma cell line, SMMC-7721.
Methods: Experimental samples were divided into 4 groups as follows: Group A - blank cell group (SMMC-7721); group B - low, medium, and high LPS concentration groups (1 ng/mL; 10 ng/mL; and 100 ng/mL, respectively); group C - β2GPI transfected group; and group D - β2GPI + low, medium, or high concentrations from the LPS affected group. Activation of NF-κB was evaluated using laser scanning confocal microscopy. Expression of downstream factors was measured by ELISA.
Results: Degrees of NF-κB activation in groups B, C, and D were varied. NF-κB activation in group D was the most significant, and the expressions of downstream factors, TNF-α and IL-1β, were the highest level of activation among the groups (p < 0.05), showing an LPS dose-dependency.
Conclusions: LPS enhanced the signal transduction of β2GPI in liver cancer cells leading to activation of NF-κB, which triggered downstream signal transduction and increased the expression of downstream factors. This suggests that LPS enhancement of β2GPI signal transduction may play a role in promoting the development of liver cancer.
DOI: 10.7754/Clin.Lab.2015.150109
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