Dataset Information

Bacterial translocation aggravates CCl₄-induced liver cirrhosis by regulating CD4⁺ T cells in rats.

ABSTRACT: Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3⁺CD4⁺CD25⁺Foxp3⁺), Th17 (CD3⁺CD4⁺IL-17⁺), and Th1 (CD3⁺CD4⁺IFN-?⁺) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl₄. We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT. We found that BT may cause increase of Treg cells in the proximal small intestine and decrease of Th17 cells in the whole intestine and blood in cirrhotic rats. It may also aggravate the CCl₄-induced decrease in Th1 cells in the whole intestine, liver, caecum, and blood and the CCl₄-induced increase in Th17 cells in the liver and Tregs in the distal small intestine, colon, and liver. Our data suggest that BT may aggravate liver injury and decrease liver function via an interaction with CD4⁺ T Cells. The results of this study may be helpful for the development of new treatments for liver cirrhosis.

SUBMITTER: Shi H

PROVIDER: S-EPMC5278361 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Bacterial translocation aggravates CCl4-induced liver cirrhosis by regulating CD4+ T cells in rats.

Shi Haiyan H Lv Longxian L Cao Hongcui H Lu Haifeng H Zhou Ning N Yang Jiezuan J Jiang Haiyin H Dong Huihui H Hu Xinjun X Yu Wei W Jiang Xiawei X Zheng Beiwen B Li Lanjuan L

Scientific reports 20170130

Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3+CD4+CD25+Foxp3+), Th17 (CD3+CD4+IL-17+), and Th1 (CD3+CD4+IFN-γ+) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic ...[more]

PMID: 28134306

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Project description:Acute liver injury (ALI) is a global health problem associated with high mortality and has attracted clinical attention. Ginkgo biloba extract (GBE) is an extract from dried Ginkgo leaves that has many pharmacological effects because of its various ingredients and has been shown to be hepatoprotective. We investigated the hepatoprotective effect of GBE on carbon tetrachloride (CCl4)-induced acute liver injury in vitro. The components of Ginkgo biloba extract are analyzed by LC-MS, and the key targets of "liver injury-Ginkgo biloba" are identified based on bioinformatics analysis. The signaling pathways such as PI3K/AKT are mainly enriched with high correlation in KEGG. The results of in vitro experiments showed that compared with the Model group, except that the ALT activity level and MDA content in EGB-L group were not significantly decreased (P > 0.05), the activity of ALT, AST and MDA content in other EGB groups were significantly decreased (P < 0.05), and the activities of SOD and CAT were significantly increased (P < 0.05). The expression of inflammatory factors IL-1β, IL-6 and TNF-α were also detected. The results showed that compared with the Model group, the contents of IL-6 in EGB-L group were not significantly decreased (P > 0.05), while the contents of IL-1β, IL-6 and TNF-α in other EGB groups were significantly decreased (P < 0.05), indicating that EGB could reduce the level of cell inflammation. Western blot assay detected the protein expression levels of GF, RTK, PI3K, AKT and p-AKT in cells. The results showed that compared with the Model group, the protein expression levels of GF, RTK, PI3K, AKT and P-AKT were significantly increased after EGB treatment (P < 0.05), and the protein expression level of the EGB-H group was higher than the EGB-L group. Ginkgo biloba extract can inhibit the expression of downstream related genes by activating PI3K/AKT signaling pathway, and at the same time alleviate the inflammatory response of cells, reduce the level of inflammation, and protect the cell damage caused by CCl4.

Project description:BackgroundExperimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD).MethodsPatients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of acute decompensation or infections were included (n = 249). Serum biomarkers of BT (lipopolysaccharide [LPS], lipoteichoic acid [LTA], bacterial DNA [bactDNA]), systemic inflammation and markers of circulatory dysfunction were assessed. T-cell subsets in intestinal biopsies (n = 7 ACLD, n = 4 controls) were analyzed by flow cytometry.ResultsPatients had a median HVPG of 18 (12-21) mmHg and 56% had decompensated ACLD. LPS (0.04 [0.02-0.06] vs. 0.64 [0.30-1.06] EU/mL), LTA (4.53 [3.58-5.97] vs. 43.2 [23.2-109] pg/mL), and detection of bactDNA (≥ 5 pg/mL; 5% vs. 41%) were markedly higher in patients with ACLD than healthy controls (n = 40; p < 0.001) but were similar between different clinical stages of compensated and decompensated ACLD and displayed no meaningful correlation with HVPG and systemic hemodynamics. TNF-α and IL-10 correlated with LPS (Spearman's rs = 0.523, p < 0.001/rs = 0.143, p = 0.024) but not with LTA. Presence of bactDNA was associated with higher LPS (0.54 [0.28-0.95] vs. 0.88 [0.32-1.31] EU/mL, p = 0.001) and TNF-α (15.3 [6.31-28.1] vs. 20.9 [13.8-32.9] pg/mL). Patients with ACLD exhibited a decreased CD4:CD8-ratio and increased TH1-cells in the intestinal mucosa as compared to controls. During a median FU of 14.7 (8.20-26.5) months, bacterial antigens did not predict decompensation or liver-related death (in contrast to HVPG, IL-6, and MAP) as well as infections at 24 months.ConclusionBT occurs already in early ACLD stages and triggers a systemic inflammatory response via TNF-α and IL-10. Interestingly, BT markers showed no clear correlation with portal hypertension and circulatory dysfunction in patients with stable ACLD.Clinical trial numberNCT03267615.

Dataset Information

Bacterial translocation aggravates CCl₄-induced liver cirrhosis by regulating CD4⁺ T cells in rats.

Publications

Bacterial translocation aggravates CCl<sub>4</sub>-induced liver cirrhosis by regulating CD4<sup>+</sup> T cells in rats.

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