IL-6 induced angiotensinogen expression in primary cultures of mouse hepatocytes.

<p>(A) Time course of IL-6-induced (10 ng/ml) angiotensinogen protein expression as detected by enzyme immunoassay (n = 3/group). (B) Dose response of IL-6-induced angiotensinogen protein expression after 24 hours of culture, as detected by enzyme immunoassay. Comparisons are between the indicated groups. *<i>P</i><0.05, n = 3.</p

Effect of IL-6-related signaling inhibition on angiotensinogen protein expression and liver regeneration in remnant livers after 70% partial hepatectomy in mice.

<p>Mice were pretreated with chemical inhibitors of JAK2 (AG490, 10 mg/kg subcutaneously), p38 (intraperitoneal SB203580, 15 mg/kg), and STAT3 (intraperitoneal 5,15-DPP, 15 mg/kg) for 4 hours prior to partial hepatectomy. (A) Serum angiotensinogen levels of mice pretreated with different chemical inhibitors (AG490, SB203580, and 5,15-DPP) as detected by enzyme immunoassay. (B) Changes in the ratio of remnant to original liver weight after 70% partial hepatectomy. Remnant liver weight was estimated retrospectively from the excised liver weight after 70% PH. Data are presented as mean ± S.D., and comparisons were made between groups as indicated. *<i>P</i><0.05. (C) Ki-67 staining of regenerated liver tissue sections of the indicated group. Magnification, 400x. (D) Quantification of Ki-67 staining. Data presented here are the quantification of Ki-67-positive nuclei per high-power field. Data are presented as mean percentage of positive nuclei ± S.D., and comparisons were made between groups as indicated. *<i>P</i><0.05.</p

Signal transduction pathways involved in IL-6-induced angiotensinogen expression in primary cultures of mouse hepatocytes.

<p>(A) Inhibition effects of chemical inhibitors 1 to 6 on IL-6-activated signaling mediators detected by Western blotting and quantified by calculating the ratios of phosphorylated/non-phosphorylated protein forms. The ratio in lane 1 is defined as 1. Comparison is between lanes 2 and 3 in each group. *<i>P</i><0.05, n = 3. (B) The effects of different chemical inhibitors on IL-6-induced angiotensinogen protein expression as detected by enzyme immunoassay. Comparison is between the indicated groups. *<i>P</i><0.05, n = 3.</p

Serum IL-6 and angiotensinogen levels, angiotenisogen mRNA and protein expression in remnant livers after 70% partial hepatectomy in mice.

<p>(A) Serum angiotensinogen levels detected by enzyme immunoassay (n = 5/group). (B) Angiotensinogen mRNA detected by reverse transcription-polymerase chain reaction quantified by calculating the ratios of angiotensinogen/GAPDH. (C) Angiotensinogen protein expression detected by Western blot and quantified by calculating the ratios of angiotensinogen/ß-actin. The ratio in lane 1 is defined as 1. Comparison is between the time 0 group and specified time periods. *<i>P</i><0.05, n = 5.</p

Schematic for LPA enhanced expression of angiogenesis factors, cytokines, and chemokines in liver sinusoidal endothelial cells mediated by LPAR1 and LPAR3 signaling.

<p>Schematic for LPA enhanced expression of angiogenesis factors, cytokines, and chemokines in liver sinusoidal endothelial cells mediated by LPAR1 and LPAR3 signaling.</p

LPA effects on angiogenesis factor, cytokine, and chemokines expression are mediated by LPAR1 and LPAR3 signaling.

<p>(A) LPAR1 and LPAR3 signaling effects on LPA induced proteins level. Liver sinusoidal endothelial cells were pre-treated with an inhibitor of LPAR1 and LPAR3, ki16425 (1 uM), for 30 minutes prior 5 uM LPA treatment. After 24 hours, conditioned media derived from vehicle (1% BSA), LPA (5uM) alone, and ki16425 plus LPA treatment were collected for protein level determinations by EIA. Data shown are fold changes of induction with LPA alone versus vehicle treatment, and ki16425 treatment combined with LPA versus vehicle treatment. Results were compared between LPA treatment alone and ki16425 treatment combined with LPA (n = 3); *<i>p</i> < 0.05. (B) Time course for LPA effects on specific genes’ mRNA expressions. Liver sinusoidal endothelial cells were treated with vehicle (1% BSA) or LPA (5 uM). After 4, 8, and 16 hours, total RNA was isolated from vehicle and LPA treated cells for mRNA determinations by qRT-PCR. Data are fold changes of induction with LPA treatment versus vehicle treatment. Results were compared with vehicle treatment (n = 3); *<i>p</i> < 0.05.</p