Protection against Acute Hepatocellular Injury Afforded by Liver Fibrosis Is Independent of T Lymphocytes

Abstract

Collagen produced during the process of liver fibrosis can induce a hepatocellular protective response through ERK1 signalling. However, the influence of T cells and associated cytokine production on this protection is unknown. In addition, athymic mice are frequently used in hepatocellular carcinoma xenograft experiments but current methods limit our ability to study the impact of liver fibrosis in this setting due to high mortality. Therefore, a mouse model of liver fibrosis lacking T cells was developed using Foxn1 nu/nu mice and progressive oral administration of thioacetamide (TAA) [0.01–0.02%] in drinking water. Fibrosis developed over a period of 16 weeks (alpha-SMA positive area: 20.0 ± 2.2%, preCol1a1 mRNA expression: 11.7 ± 4.1 fold changes, hydroxyproline content: 1041.2 ± 77μg/g of liver) at levels comparable to that of BALB/c mice that received intraperitoneal TAA injections [200 μg/g of body weight (bw)] (alpha-SMA positive area: 20.9 ± 2.9%, preCol1a1 mRNA expression: 13.1 ± 2.3 fold changes, hydroxyproline content: 931.6 ± 14.8μg/g of liver). No mortality was observed. Athymic mice showed phosphorylation of ERK1/2 during fibrogenesis (control 0.03 ± 0.01 vs 16 weeks 0.22 ± 0.06AU; P<0.05). The fibrosis-induced hepatoprotection against cytotoxic agents, as assessed histologically and by serum AST levels, was not affected by the absence of circulating T cells (anti-Fas JO2 [0.5μg/g bw] for 6h (fibrotic 4665 ± 2596 vs non-fibrotic 13953 ± 2260 U/L; P<0.05), APAP [750 mg/kg bw] for 6 hours (fibrotic 292 ± 66 U/L vs non-fibrotic 4086 ± 2205; P<0.01) and CCl4 [0.5mL/Kg bw] for 24h (fibrotic 888 ± 268 vs non-fibrotic 15673 ± 2782 U/L; P<0.001)). In conclusion, liver fibrosis can be induced in athymic Foxn1 nu/nu mice without early mortality. Liver fibrosis leads to ERK1/2 phosphorylation. Finally, circulating T lymphocytes and associated cytokines are not involved in the hepatocellular protection afforded by liver fibrosis.

Serum analysis method combining cellulose acetate membrane purification with surface‐enhanced Raman spectroscopy for non‐invasive HBV screening

“…In addition, the SERS band of amide III at 1261 cm −1 in serum protein of HBV patients groups shows higher signal intensity than in normal samples, because the amide III band has been shown to be sensitive to protein secondary structure [21]. The prominent SERS peak located at around 1207 cm −1 is ascribed to the appearance of hydroxyproline, as an important product of collagen metabolism, whose content is associated with the development of liver fibrosis (as a complication of HBV infection) [22, 23]. The SERS peak of phenylalanine at 1007 cm −1 and the ring breathing of tyrosine at 1160 and 1178 cm −1 showed higher normalised intensity in the HBV patients groups.…”

Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells

“…In terms of T cells, different T-cell subpopulations play different roles in the process of liver fibrosis. Previous studies have reported that T-cell impairment generally does not alter fibrogenesis, while Th2 and Th17 CD4 + T cells are involved in the inflammatory process, promoting cytokine production and HSC activation[ 36 ]. Here, the ratio of CD4 + T cells and CD8 + T cells was upregulated in the liver and spleen (data not shown), but the activation of these T cells was not significantly affected by Fasudil treatment (Figure 3 ).…”