ABSTRACT
BACKGROUND: B cell-activating transcription factor (BATF) contributes to Th17 cell differentiation and pathological inflammatory responses. AIMS: This study explored BATF as a regulator of Th17 differentiation in normal and hepatitis B virus (HBV) transgenic mice. METHODS: Normal mice were divided into control, short hairpin RNA (shRNA) scramble, and shRNA BATF groups. HBV transgenic mice were divided into control, entecavir, shRNA scramble, entecavir + vector control, entecavir + shRNA scramble, shRNA BATF, and entecavir + shRNA BATF groups. Serum concentrations of AST, ALT, HBV-DNA, BATF, IL-17, and IL-22 and Th17 cell frequencies in the liver were compared among the groups. Correlations of serum HBV surface antigen (HBsAg), e-antigen (HBeAg), and core antigen (HBcAg) concentrations with BATF mRNA expression and the proportion of Th17 cells in the livers of HBV transgenic mice were also analyzed. RESULTS: Serum AST, ALT, BATF, IL-17, and IL-22 concentrations and Th17 cell proportions were higher in HBV transgenic mice relative to normal controls. Positive correlations of the HBcAg concentration with BATF mRNA and the proportion of Th17 cells were observed in HBV transgenic mice. BATF interference reduced the proportion of Th17 cells and serum IL-17 and IL-22 concentrations and led to obvious downregulation of AST, ALT, BATF, IL-17, and IL-22 expression and a reduced proportion of Th17 cells when combined with entecavir. CONCLUSION: HBV markedly upregulated BATF expression and promoted Th17 cell activation. By contrast, BATF interference significantly impeded the proliferation of Th17 cells and secretion of IL-17 and IL-22 while alleviating hepatic lesions.
Subject(s)
Basic-Leucine Zipper Transcription Factors/metabolism , Cell Differentiation , Hepatitis B virus/genetics , Hepatitis B/metabolism , Liver/metabolism , Lymphocyte Activation , Th17 Cells/metabolism , Animals , Antiviral Agents/pharmacology , Basic-Leucine Zipper Transcription Factors/genetics , Cell Differentiation/drug effects , Disease Models, Animal , Guanine/analogs & derivatives , Guanine/pharmacology , Hepatitis B/immunology , Hepatitis B/prevention & control , Hepatitis B/virology , Hepatitis B virus/growth & development , Host-Pathogen Interactions , Interleukin-17/metabolism , Interleukins/metabolism , Liver/drug effects , Liver/immunology , Liver/virology , Lymphocyte Activation/drug effects , Male , Mice, Inbred BALB C , Mice, Transgenic , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Th17 Cells/drug effects , Th17 Cells/immunology , Th17 Cells/virology , Viral Load , Interleukin-22ABSTRACT
BACKGROUND: T helper (Th) 17 cells participate in the pathogenesis of liver diseases but their exact role in acute-on-chronic hepatitis B liver failure (ACHBLF) still remains obscure. AIMS: This present study was aimed to characterize the circulating Th17 cells and to analyze their association with disease progression in ACHBLF. METHODS: This retrospective study consisted of 40 ACHBLF patients, 40 chronic hepatitis B (CHB) patients and 20 healthy controls. The frequency of peripheral Th17 cells and IL-17 mRNA level in peripheral blood mononuclear cells (PBMCs) were estimated by flow cytometry and relative quantitative real-time polymerase chain reaction. RESULTS: We found that the frequency of peripheral Th17 cells, as well as the level of IL-17 mRNA in PBMCs, was significantly increased in ACHBLF patients compared with CHB patients and healthy controls. In ACHBLF patients, the frequency of Th17 cells was positively correlated with serum total bilirubin (r = 0.392, P = 0.012) and model for end-stage liver disease scores (r = 0.383, P = 0.015), but negatively correlated with prothrombin activity (r = -0.317, P = 0.046). The same trend was observed as for relative expression of IL-17. Furthermore, the frequency of Th17 cells and IL-17 mRNA level were significantly elevated in non-survivors compared with survivors in ACHBLF patients. CONCLUSIONS: These results suggested that Th17 cells as well as IL-17 might be related with disease severity and prognosis in ACHBLF patients.
Subject(s)
Hepatitis B, Chronic/immunology , Interleukin-17/genetics , Liver Failure, Acute/immunology , Th17 Cells/immunology , Adult , Biomarkers/blood , Female , Flow Cytometry , Gene Expression/immunology , Hepatitis B, Chronic/pathology , Humans , Liver Failure, Acute/pathology , Male , Middle Aged , Prognosis , RNA, Messenger/metabolism , Retrospective Studies , Severity of Illness Index , Th17 Cells/pathology , Young AdultABSTRACT
OBJECTIVE: To investigate the effect of IL-10 and the methylation of its promoter in acute on chronic liver failure (ACLF). METHODS: Patients were divided into three groups: 25 with ACLF, 25 with CHB, 10 healthy controls. Respectively detect the serum level of IL-10 via ELISA, and the methylation of IL-10 promoter via MSP, to analyze the difference among the three groups. RESULTS: Both the ACLF group and the CHB group have significant increase in serum level of IL-10 compared with the control group (P < 0.05); the ACLF group's level is higher than the CHB group, however without statistical significance (P > 0.05). The serum level of IL-10 in ACLF group has no significant relativity with ALT and HBV-DNA( r = -0.022, r = 0.033, respectively; P > 0.05); has positive relativity with TBIL and MELD ( r = 0.566, r = 0.443, respectively; P < 0.05); and negative relativity with PTA (r = -0.581, P < 0.05). The distribution of the methylation of IL-10 promoter in ACLF group is significantly different from the other two. CONCLUSION: The serum level of IL-10 in hepatitis patients is significantly higher and increases with the degree of liver failure. The promoter methylation may be important in the gene inactivation.
Subject(s)
DNA Methylation , Interleukin-10/blood , Interleukin-10/genetics , Liver Failure, Acute/metabolism , Adolescent , Adult , Chronic Disease , Female , Humans , Interleukin-10/metabolism , Liver Failure, Acute/blood , Liver Failure, Acute/genetics , Male , Methylation , Middle Aged , Promoter Regions, Genetic , Young AdultABSTRACT
OBJECTIVE: The pathogenesis of hepatitis B virus (HBV)-associated chronic liver disease is still not fully understood. The immune imbalance of cytokine profile exerts a profound influence on the resolution of HBV infections and HBV clearance. This present study aimed to evaluate the immune status of the peripheral T helper (Th) 17 and Th1 cells in the active patients with chronic HBV infection. MATERIALS AND METHODS: Thirty patients with chronic active hepatitis B were included in our present study. The frequency of peripheral Th 17 cells (CD3(+)CD8(-)IL-17(+) T cells), Th1 cells (CD3(+)CD8(-)IFN-gamma(+) T cells), and Tc1 cells (CD3(+)CD8(+)IFN-gamma(+) T cells) in chronic hepatitis B (CHB) were analyzed by flow cytometry. The protein and mRNA levels of interleukin-17 (IL-17) and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (PCR). RESULTS: The percentage of Th17 cells in peripheral blood of CHB patients (1.53 +/- 0.52%) was significantly increased than that in normal controls (0.92 +/- 0.20%; P < 0.05). In contrast, the percentage of Th1 and Tc1 cells of CHB patients was significantly decreased as compared with that of control group. The frequency of Th17 cells had a negative correlation with Th1 cells, and a positive correlation with serum alanine aminotransferase in CHB patients. CONCLUSION: The elevated peripheral Th17 cells were obtained in the patient with chronic active hepatitis B, suggesting its potential role in the immune activation of chronic HBV infection.
