Using luciferase-expressing human hepatoma cells, Naka and Fujimoto demonstrated that combinatorial stimulation with IL-6 and IL1-β, which respectively signal through the transcription factors STAT3 and NFkB, has a synergistic effect on the activity of the Lrg1 promoter, thus confirming the hypothesis that Lrg1 expression can be boosted by the co-presence of multiple cytokines [30]. This evidence concerns the gene IL1B and hepatocellular carcinoma.