Lipopolysaccharide Enhances Beta2-Glycoprotein I Activation of Nuclear Factor κB in Liver Cancer Cells

Background: Beta2-glycoprotein I (beta(2)GPI) is a highly abundant glycoprotein in plasma. Our previous study demonstrated strong beta(2)GPI expression in hepatitis B-related hepatocellular carcinoma (HCC) tissue and the combination of beta(2)GPI and hepatitis B surface antigen (HBsAg) was shown to significantly activate the nuclear factor kappa B (NF-kappa B). To investigate whether lipopolysaccharide (LPS) enhances beta(2)GPI activation of NF-kappa B and the expression of downstream factors (e.g., tumor necrosis factor alpha, TNF-alpha; interleukin-1 beta, IL-1 beta; 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 - beta(2)GPI transfected group; and group D - beta(2)GPI + low, medium, or high concentrations from the LPS affected group. Activation of NF-kappa B was evaluated using laser scanning confocal microscopy. Expression of downstream factors was measured by ELISA. Results: Degrees of NF-kappa B activation in groups B, C, and D were varied. NF-kappa B activation in group D was the most significant, and the expressions of downstream factors, TNF-alpha and IL-1 beta, were the highest level of activation among the groups (p < 0.05), showing an LPS dose-dependency. Conclusions: LPS enhanced the signal transduction of beta(2)GPI in liver cancer cells leading to activation of NF-kappa B, which triggered downstream signal transduction and increased the expression of downstream factors. This suggests that LPS enhancement of beta(2)GPI signal transduction may play a role in promoting the development of liver cancer.