Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice.

Abstract

AIM:

To investigate the effect of T helper (Th) 17/T regulatory (Treg) cells on hepatic fibrosis in mice and its possible mechanism.

METHODS:

Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. Hepatic pathological changes were observed by hematoxylin and eosin staining; the protein levels of interleukin (IL)-6, transforming growth factor (TGF)-β and α-smooth muscle actin (SMA) in liver tissue were determined by Western blotting; and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry. In addition, hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells. Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation.

RESULTS:

In the model group, there were different degrees of fibroplasia, degeneration and necrosis. The protein levels of IL-6, TGF-β and α-SMA in liver tissue were significantly higher than those in the control group at 12 wk (P < 0.05). Compared with the control group, the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually. Furthermore, at 4, 8 and 12 wk, there were significant differences in the number of Th17 cells (0.52% ± 0.16%, 1.46% ± 0.24%, and 2.60% ± 0.41%, respectively, P < 0.05) and Treg cells (2.99% ± 0.40%, 2.16% ± 0.50%, and 1.49% ± 0.34%, respectively, P < 0.05). In vitro, Th17 cells promoted, whereas Treg cells inhibited the expression of α-SMA, both in a dose-dependent manner, compared with the control group.

CONCLUSION:

Th17/Treg imbalance exists in mice with liver fibrosis, which potentially promotes liver fibrosis via HSC activation.

• Authors: Xiao-Fei Sun, Lei Gu, Wen-Sheng Deng, Qing Xu
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 8 Pg. 2062-70 (Feb 28 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 24616573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Interleukin-6
• Transforming Growth Factor beta
• Carbon Tetrachloride

Topics

• Actins (metabolism)
• Animals
• Carbon Tetrachloride (toxicity)
• Flow Cytometry
• Hepatic Stellate Cells (cytology)
• Interleukin-6 (metabolism)
• Liver (metabolism, pathology)
• Liver Cirrhosis (chemically induced, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Microscopy, Fluorescence
• T-Lymphocytes, Regulatory (cytology)
• Th17 Cells (cytology)
• Transforming Growth Factor beta (metabolism)