Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a series of in vivo experiments to clarify the hepatoprotective activity of green tea against lipopolysaccharide (LPS) + D-galactosamine (GalN)-induced liver injury and to elucidate the mechanism by which green tea exerts its effect in 7-wk-old male Wistar rats. Liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities. Green tea extract significantly suppressed LPS + GalN-induced liver injury when added to the diet (30 or 35 g/kg) and fed to rats for 14 d or when force-fed alone (0.4-1.2 g/kg body) 1.5 h before the injection of drugs. Although all five of the fractions extracted from green tea extract with different organic solvents had significant suppressive effects, the caffeine-containing fraction exhibited the strongest effect, suggesting that the protective effect of green tea against LPS + GalN-induced liver injury is attributable mainly to caffeine. Authentic caffeine also significantly suppressed LPS + GalN-induced liver injury when added to the diet (2 g/kg) and fed to rats for 14 d. Dietary green tea suppressed LPS + GalN-induced apoptosis of liver cells, as assessed by DNA fragmentation. However, dietary green tea did not suppress LPS-induced enhancement of plasma concentration of tumor necrosis factor (TNF)-alpha, the cytokine that is thought to play a pivotal role in the pathogenesis of LPS-induced liver injury, although it significantly suppressed plasma concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10 and interferon (IFN)-gamma. TNF-alpha + GalN-induced liver injury and apoptosis were also suppressed by dietary green tea. In contrast, dietary caffeine significantly suppressed LPS-induced enhancement not only of plasma IL-1beta, IL-6, IL-10 and IFN-gamma concentrations, but also of TNF-alpha concentration. The results suggest that green tea might suppress LPS + GalN-induced liver injury mainly through the inhibition of TNF-alpha-induced apoptosis of hepatocytes, rather than through the suppression of TNF-alpha production, although the suppressed production of TNF-alpha may be associated with the hepatoprotective effect of caffeine.
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PMID:Green tea suppresses lipopolysaccharide-induced liver injury in d-galactosamine-sensitized rats. 1134 Jan 16

A mechanism of liver injury such as, viral hepatitis or autoimmune hepatitis is considered to involve the impairment of hepatocytes mainly mediated by T-cell immunity, but the roles of a variety of cytokines involved in regulation remain unclarified. We investigated the involvement of various cytokines, particularly, interleukin-10 (IL-10) which is considered to be an anti-inflammatory cytokine, in a murine model of experimental liver injury induced by Concanavalin A (Con A). The model of liver injury was made by intravenous injection of Con A (0.5 &mgr;g) through the caudal vein in 6-week-old female BALB/c mice weighting 20 g. By collecting blood before and at 1, 3, 6, 12 and 24 h after the injection of Con A, alanine aminotransferase (ALT) levels were sequentially measured, and liver tissue was sampled to examine liver injury. Furthermore, TNF-alpha, IL-4 and IL-10 levels were sequentially determined by enzyme-linked immunosorbent assay (ELISA). Serum ALT significantly increased between 3 and 24 h after the Con A injection, and spotty necrosis was histologically observed, suggesting mild liver injury. TNF-alpha and IL-4 increased soon after the injection of Con A. IL-10 increased bimodally soon after and at 12 h after the Con A injection. After neutralizing antibodies (1 &mgr;g) to IL-10 were intraperitoneally injected into the same model at 6 h before Con A treatment, serum ALT levels and the histology of the liver were examined 12 h after the Con A injection. ALT was significantly higher in the group treated with anti-IL-10 antibody (130.7+/-33.5 IU per I) than in the non-treated group (56.5+/-3.5 IU per I) (P<0.05). Histological examination showed spotty necrosis in the group treated with anti-IL-10 antibody. These results suggest that IL-10 has inhibitory effect on liver injury in a murine model of Con A-induced experimental liver injury mediated by cellular immunity.
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PMID:Involvement of IL-10, an anti-inflammatory cytokine in murine liver injury induced by Concanavalin A. 1134 58

Interferon regulates the activity of other cytokines. Alterations in non-specific immune response, particularly cytokine level changes result in therapeutic difficulties in patients with chronic hepatitis C. Serum levels of IL-1 beta, IL-2, IL-4, IL-6 and IFN-gamma were measured in patients with chronic hepatitis C before the interferon therapy, in the early phase of the treatment (after the 6th dose of the drug), and in the later stable phase of the treatment (after the 36th dose of the drug). Concentrations of cytokines during the interferon therapy were compared to the changes in alanine aminotransferase activity. The IL-1 beta, IL-2, IL-4 and IL-6 serum concentrations were initially elevated in all patients. The increase in IL-1 beta level after the 6th dose and the decrease after 36th dose of IFN appeared to be an indicator of a good response to treatment. High levels of IL-6 before the IFN therapy followed by a decrease after the 6th dose and high levels of IL-4 followed by a decrease after 36th IFN dose also indicated good response. High levels of IL-2, stable throughout the treatment suggested a poor response. No changes in the IFN-gamma values before or during the treatment were observed.
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PMID:The levels of IL-1 nu beta, IL-2, IL-4, IL-6 and IFN-gamma among patients with chronic hepatitis type C treated with IFN-alpha. 1171 33

Fumonisin B1 (FB1), a mycotoxin produced primarily by Fusarium veticillioides and related fungi, is a carcinogen and causative agent of various animal diseases. Our previous studies indicated the involvement of tumor necrosis factor-alpha (TNFalpha) in FB1-induced hepatotoxicity. Male B6,129 mice (five/group) were injected subcutaneously with vehicle or 2.25 mg/kg/day of FB1 for 5 days and sampled 1 day after the last treatment. FB1 treatment caused an increased expression of TNFalpha, interferon gamma (IFNgamma) and interleukin (IL)-12 p40 in liver without any changes in kidney or spleen, suggesting the localized site of their production. IL-1beta cytokine expression was increased in liver and kidney after FB1 exposure. Cells involved in TNFalpha production after FB1 treatment in liver were identified as Kupffer cells. FB1 increased alanine aminotransferase in plasma and increased apoptotic cells in liver. Selective increase in proinflammatory T helper (Th)1-cytokines (IL-12 and IFNgamma) and TNFalpha with no alteration in Th2-cytokines (IL-4, IL-6 and IL-10) suggest the involvement of IL-12, produced by Kupffer cells, in induction of IFNgamma production by natural killer (NK) cells and/or NK1+ T cells, which can undergo a positive amplification loop with TNFalpha produced by macrophages or other hepatic cells to elicit the toxic reaction.
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PMID:Fumonisin B1-induced localized activation of cytokine network in mouse liver. 1238 13

The immunoregulatory roles of interleukin-2 (IL-2), IL-4, IL-10, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), the soluble form of the IL-2 receptor (sIL-2R), and the soluble form of CD30 (sCD30) were evaluated in patients with hepatitis B virus (HBV) infection. Two groups of subjects were studied: 15 healthy individuals without hepatitis antecedents and 15 patients with HBV infection. Blood samples were taken during the acute and convalescent phases. The analysis of the samples was done by the enzyme-linked immunosorbent assay technique. IFN-gamma and TNF-alpha levels decreased in the convalescent phase. IL-10, IL-2, and sIL-2R levels increased in the acute and convalescent phases, while sCD30 levels increased during the acute phase. The IL-4 concentrations decreased in both phases. During the acute phase, IFN-gamma and TNF-alpha induced increases in IL-2, sIL-2R, IL-10, and sCD30 levels in serum, which allowed the development of immunity characterized by the nonreactivity of the HBV surface antigen, the onset of antibodies to the HBV surface antigen (anti-HBs), and normal alanine aminotransferase levels during the convalescent phase. Increased IL-2 levels during the acute phase would stimulate the activities of NK cells and CD8(+) lymphocytes, which are responsible for viral clearing. The raised sIL-2R levels reveal activation of T lymphocytes and control of the IL-2-dependent immune response. The sCD30 increment during the acute phase reflects the greater activation of the Th2 cellular phenotype. Its decrease in the convalescent phase points out the decrease in the level of HBV replication. The increase in IL-10 levels could result in a decrease in IL-4 levels and modulate IFN-gamma and TNF-alpha levels during both phases of disease, allowing the maintenance of anti-HBs concentrations.
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PMID:Concentrations of cytokines, soluble interleukin-2 receptor, and soluble CD30 in sera of patients with hepatitis B virus infection during acute and convalescent phases. 1241 77

We recently reported that the direct antitumor effectors in the liver induced by alpha-galactosylceramide (alpha-GalCer) are NK cells that are activated by the IFN-gamma produced from NK1.1 Ag(+) T cells (NKT cells) specifically stimulated with alpha-GalCer, whereas NKT cells cause hepatocyte injury through the Fas-Fas ligand pathway. In the present study, we investigated how mouse age affects the alpha-GalCer-induced effect using young (6-wk-old), middle-aged (30-wk-old), and old (75-wk-old) mice. The serum IFN-gamma and IL-4 concentrations as well as alanine aminotransferase levels after the alpha-GalCer injection increased in an age-dependent manner. An alpha-GalCer injection also induced an age-dependent increase in the Fas ligand expression on liver NKT cells. Under the stimulus of alpha-GalCer in vitro, the liver mononuclear cells from old and middle-aged mice showed vigorous proliferation, remarkable antitumor cytotoxicity, and enhanced production of both IFN-gamma and IL-4 in comparison to those of young mice, all of which were mediated mainly by NK1.1(+) cells. Furthermore, liver mononuclear cells from old mice stimulated with alpha-GalCer showed a more potent Fas-Fas ligand-mediated cytotoxicity against primary cultured hepatocytes than did those from young mice. Most alpha-GalCer-injected old mice, but no young mice, died, while anti-IFN-gamma Ab pretreatment completely inhibited mouse mortality. However, alpha-GalCer-induced hepatic injury did not improve at all by anti-IFN-gamma Ab treatment, and the Fas-ligand expression of liver NKT cells did not change. Taken together, the synthetic ligand-mediated function of NKT cells is age-dependently up-regulated, and the produced IFN-gamma is responsible for alpha-GalCer-induced antitumor immunity and the mouse mortality, while hepatic injury was unexpectedly found to be independent of IFN-gamma.
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PMID:Age-associated augmentation of the synthetic ligand- mediated function of mouse NK1.1 ag(+) T cells: their cytokine production and hepatotoxicity in vivo and in vitro. 1244 15

BACKGROUND AND AIM: Thymosin-alpha1 (T-alpha1) influences T-cell maturation, production of Th1-type cytokines, and activity of NK cell-mediated cytotoxicity. The aim of this study is to evaluate the types of lymphocytes that contribute to the reduction in viral load in patients with chronic hepatitis B (CHB) following T-alpha1 treatment. METHODS: Seven patients with CHB were treated with 1.2 mg of T-alpha1 for 24 weeks. Peripheral blood lymphocytes (PBL) and intrahepatic lymphocytes were analyzed by flow cytometry. Serum cytokines (IL-4 and IFN-gamma) were measured by ELISA. RESULTS: Forty-eight weeks after T-alpha1 treatment, two patients (28.6%) showed normalized alanine aminotransferase and decreased HBV-DNA to undetectable level from serum. The histology activity index score significantly decreased (P<0.05). Although elevated serum interferon (IFN)-gamma was not observed, IFN-gamma producing Th1-type CD4(+) PBL appeared to be increased. CD56(+) natural killer T (NKT) cells in PBL did not increase, these cells in the liver remained significantly augmented even at the end of treatment (P<0.05). CD57(+) NKT cells slightly increased and the ratio of CD4(+) T/CD8(+) T cells decreased in the liver. T-alpha1 did not influence either double-positive CD4(+)8(+) T or double-negative CD4(-)8(-) cell subsets. CONCLUSION: NKT cells and CD8(+) cytotoxic T lymphocytes augmented in the liver by T-alpha1 may eliminate hepatitis B virus infected hepatocytes.
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PMID:Thymosin-alpha1 increases intrahepatic NKT cells and CTLs in patients with chronic hepatitis B. 1247 32

BACKGROUND/AIMS: Bovine lactoferrin (bLF) has been shown to prevent the infection of cultured hepatocytes by hepatitis C virus (HCV). The present study attempted to clarify the effects of long-term administration of bLF on serum parameters, including immunomodulatory cytokines, in patients with chronic hepatitis C (CHC). METHODS: Sixty-three CHC patients were randomly assigned into 2 groups. At an oral dose of 600 mg/day, bLF was administered for 12 months to 36 patients (bLF group), while no bLF was given to the remaining 27 patients (control group. Serum levels of alanine aminotransferase, HCV-RNA, IL-10, and IL-18 were evaluated, as well as CD4-positive T cell subsets in the peripheral blood. RESULTS: The serum IL-18 level was increased by bLF administration, but not in the control group. After 3 months of bLF treatment, it was significantly higher than before bLF administration, but it decreased gradually thereafter. The percentage of interferon (IFN)-gamma+ and IL-4- (Th1) cells in the peripheral blood increased along with the serum IL-18 level, although the change was not statistically significant. The other parameters did not change significantly during the study period in both groups. CONCLUSIONS: These results suggest that oral administration of bLF to CHC patients for up to 3 months can produce a Th1-cytokine dominant environment in the peripheral blood that favors the eradication of HCV by IFN therapy.
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PMID:Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months. 1269 43

BACKGROUND/AIM: Concanavalin A (Con A) activates T cells and causes T cell-mediated liver injury in mice. Since autoimmune diseases predominantly occur in women, female is considered to have enhanced immune responses and T cell functions. We investigated the presence of gender-related differences on Con A-induced liver injury and cytokine production in mice. METHODS: Male and female BALB/c mice were given Con A (15mg/kg) intravenously at 7 weeks of age. Plasma alanine aminotransferase (ALT), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-10 levels were determined 0, 2, 4, 6, 8 and 24h after Con A administration. To investigate the effects of sex hormones on liver injury and cytokine production, female and male mice were castrated at 3 weeks of age and were administered Con A 4 weeks after the operation. RESULTS: Plasma ALT level of females was significantly higher at 8 and 24h after Con A administration than those of males. Plasma levels of TNF-alpha and IFN-gamma at 2, 4, 6 and 8h, IL-4 at 2h, but not IL-10, after Con A administration were significantly elevated in females than those of males. Furthermore, the elevated plasma ALT, TNF-alpha and IFN-gamma levels decreased significantly by an ovariectomy. In contrast, those markers were exacerbated by an orchiectomy compared with sham operation. CONCLUSION: These findings indicate that Con A induces more severe liver injury in female mice than in male mice, and suggest that the effect of sex hormones on cytokine production may play a role in gender-related difference on Con A-induced liver injury.
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PMID:Gender-related differences in concanavalin A-induced liver injury and cytokine production in mice. 1458 99

Administration of Con A induces liver injury that is considered to be an experimental model for human autoimmune or viral hepatitis, where immunopathology plays roles mediated by activated lymphocytes, especially NK1.1+ CD3+ NKT cells, and inflammatory cytokines, including IFN-gamma and IL-4. In the present study we investigated the role of WSX-1, a component of IL-27R, in Con A-induced hepatitis by taking advantage of WSX-1 knockout mice. WSX-1-deficient mice were more susceptible to Con A treatment than wild-type mice, showing serum alanine aminotransferase elevation and massive necrosis in the liver. Although the development of NKT cells appeared normal in WSX-1 knockout mice, purified NKT cells from the knockout mice produced more IFN-gamma and IL-4 than those from wild-type mice in response to stimulation with Con A both in vitro and in vivo. In addition, hyperproduction of proinflammatory cytokines, including IL-1, IL-6, and TNF-alpha, was observed in the knockout mice after Con A administration. These data revealed a novel role for WSX-1 as an inhibitory regulator of cytokine production and inflammation in Con A-induced hepatitis.
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PMID:Hyperproduction of proinflammatory cytokines by WSX-1-deficient NKT cells in concanavalin A-induced hepatitis. 1500 60


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