TLR4 SNPs reduce mHSC growth and enhance growth inhibition by pathways inhibitors. TLR4−/− mHSC lines that were stably reconstituted with human TLR4 cDNAs were treated with PI3K inhibitor (LY 294002), ERK inhibitor (PD 98059), or NF-κB inhibitor (20 μM, 10 μM, and 5 μM, respectively). DNA synthesis was assessed by 3[H]-incorporation. (A) DNA synthesis in TLR4−/− mHSCs transfected with human TLR4 WT or SNP cDNAs and MyD88−/− HSCs reconstituted with human TLR4 WT. (B) Growth reduction rate following addition of a PI3K inhibitor, ERK inhibitor, or NF-κB inhibitor. Cells with either single or dual SNPs had slower cell growth and more growth reduction following pathway inhibition than WT TLR4 cells. Each column represents the mean ± SEM of n = 6 per group in three independent experiments. *P < 0.05 when compared with the WT TLR4 cDNA-transfected HSCs.