Extracellular histones stimulate collagen expression in vitro and promote liver fibrogenesis in a mouse model via the TLR4-MyD88 signaling pathway

Figure 4 TLR4 is involved in histone-enhanced collagen I production and CCl₄-induced mouse liver fibrosis. A: LX2 cells were treated with 5 μg/mL histones (Hist) in the presence or absence of TLR4 neutralizing antibody (TLR4i). The mean ± SD of the relative percentage of collagen Ι/β-actin ratios are presented with control (UT) set at 100% from three independent experiments. ANOVA test, ^aP < 0.05 compared to UT. ^bP < 0.05 compared to histone alone; B: Typical images of Sirius red staining of liver section from untreated wt C57BL/6j mice (a), CCl₄-treated wt mice (b), and TLR4 and MyD88 knockout mice; C: The mean ± SD of stained areas of liver sections from untreated wt mice (UT), CCl₄-treated wt mice (WT), CCl₄-treated TLR4^-/- and MyD88^-/- mice. Eight mice were in each group and six sections from each mouse were analyses. ANOVA test, ^aP < 0.05 compared to untreated wt mice (UT). ^bP < 0.05 compared to CCl₄-treated wt mice. ANOVA: Analysis of variance; wt: Wild type; UT: Control.