Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previ...Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was.to characterize the TLR4 expression in peripheral blood mononuclear cells （PBMCs） of ACLF pa- tients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected （CHB） patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 ex- pression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was ana- lyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expres- sion of TLR4 on CD4＋ and CD8＋ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4＋ and CD8＋T cells were positively correlated with serum total bilirubin （TBIL）, direct bilirubin （DBIL）, international normalized ratio （INR） levels and white blood cells （WBCs）, and negatively correlated with serum albumin （ALB） levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4＋ T cells, which was also posi- tively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.展开更多
In order to investigate the immunological damage in rat immunized with AT1-receptor peptide, 18 male Wistar rats were divided into two groups: immunized-group (n=12), each rat was immunized with 150 μg AT 1-receptor...In order to investigate the immunological damage in rat immunized with AT1-receptor peptide, 18 male Wistar rats were divided into two groups: immunized-group (n=12), each rat was immunized with 150 μg AT 1-receptor petide coupled to bovine serum albumin, together with Freund's adjuvant. Control group (n=6), sham-immunized, 'immunized liquid' was same as immunized-group except AT1-receptor peptide. Systolic blood pressure (SBP) was measured by using the tail-cuff technique, antibody against AT1-receptor peptide detected by using ELISA method, and left ventricular myocardium and renal cortex sections were observed under light and electron microscopy. There was no significant difference in SBP and light microscopic observation of the tissue sections between the immunized-group and control group. The O.D. value of anti-AT1-receptor peptide antiserum was significantly higher in the immunized-group than in the rats before immunization and control group (P<0.01). Positive rate in the immunized-group was 100 %, while 0 % in the control group. Ultramicroscopic morphology showed potential myocardial injury, including: increase in number of mitochondria, swelling of many mitochondria with reduction in number or absence of their cristae and cristolysis, disorder of the cardiac myofibrils, and myofibrillar disruption and myocytolysis. And lysosomes were increased in renal tubular epithelia. The AT1-receptor peptide could induce to generate the antibody against AT1-receptor peptide and lead to myocardial and renal damage in rats.展开更多
基金supported by the National Science and Technology Major Project for Infectious Diseases of China(No.2012ZX10004503)
文摘Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was.to characterize the TLR4 expression in peripheral blood mononuclear cells （PBMCs） of ACLF pa- tients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected （CHB） patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 ex- pression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was ana- lyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expres- sion of TLR4 on CD4＋ and CD8＋ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4＋ and CD8＋T cells were positively correlated with serum total bilirubin （TBIL）, direct bilirubin （DBIL）, international normalized ratio （INR） levels and white blood cells （WBCs）, and negatively correlated with serum albumin （ALB） levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4＋ T cells, which was also posi- tively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.
文摘In order to investigate the immunological damage in rat immunized with AT1-receptor peptide, 18 male Wistar rats were divided into two groups: immunized-group (n=12), each rat was immunized with 150 μg AT 1-receptor petide coupled to bovine serum albumin, together with Freund's adjuvant. Control group (n=6), sham-immunized, 'immunized liquid' was same as immunized-group except AT1-receptor peptide. Systolic blood pressure (SBP) was measured by using the tail-cuff technique, antibody against AT1-receptor peptide detected by using ELISA method, and left ventricular myocardium and renal cortex sections were observed under light and electron microscopy. There was no significant difference in SBP and light microscopic observation of the tissue sections between the immunized-group and control group. The O.D. value of anti-AT1-receptor peptide antiserum was significantly higher in the immunized-group than in the rats before immunization and control group (P<0.01). Positive rate in the immunized-group was 100 %, while 0 % in the control group. Ultramicroscopic morphology showed potential myocardial injury, including: increase in number of mitochondria, swelling of many mitochondria with reduction in number or absence of their cristae and cristolysis, disorder of the cardiac myofibrils, and myofibrillar disruption and myocytolysis. And lysosomes were increased in renal tubular epithelia. The AT1-receptor peptide could induce to generate the antibody against AT1-receptor peptide and lead to myocardial and renal damage in rats.
