Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of neutrophils (PMNs) and PMN-dependent adhesion molecules in the pathogenesis of liver injury in a model of endotoxin shock, male ICR mice received a dose of 700 mg/kg galactosamine and 100 micrograms/kg Salmonella abortus equi endotoxin. PMNs accumulated continuously in the liver, reaching values of 446 +/- 71 PMNs/50 high-power fields at 9 h (basal value 18 +/- 7). Plasma alanine aminotransferase activities as index of parenchymal cell injury did not change up to 5 h posttreatment (basal value 35 +/- 5 U/l) but increased to 1,950 +/- 460 U/l at 9 h. The formation of glutathione disulfide (GSSG) in plasma as an index of an extracellular oxidant stress also increased only at 9 h. Pretreatment of animals with monoclonal antibodies against the CD11b and CD18 subunits of the CD11/CD18 integrin family on the surface of the PMN reduced the number of PMNs in the liver by 50% and significantly attenuated liver injury and GSSG formation. An anti-CD11a and a nonbinding control antibody were ineffective. It is concluded that PMNs are actively involved in the pathogenesis of galactosamine and endotoxin shock and that at least in part the accumulation of PMNs, the subsequent oxidant stress, and the tissue injury in this model of experimental hepatitis are CD11b/CD18 (Mac-1) dependent.
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PMID:Neutrophil-induced liver cell injury in endotoxin shock is a CD11b/CD18-dependent mechanism. 176 46

A flow cytometric phenotype for isolated adult central nervous system (CNS) ramified microglia was previously defined (CD45low CD11b/c+) in the Lewis strain rat, that clearly distinguished these cells from all blood-derived leucocytes, the latter being CD45high. Consistent with the reported lack of major histocompatibility complex (MHC) expression in the CNS, isolated microglia were mostly MHC class II-. Employing these phenotypic criteria, we now show that a proportion of microglia in Brown Norway (BN) strain rats are constitutively MHC class II+. In spinal cord, up to 25% of microglia are distinctly positive and most have some level of expression. In situ staining of MHC class II+ microglial cells in BN rats indicates that positive cells are typical of ramified microglia on the grounds of both morphological appearance and anatomical location. In Lewis (LEW) rats, the few MHC class II-expressing cells isolated from the normal CNS are CD45high blood-derived cells and not resident microglia. After infection of both LEW and BN rats with a neurotropic murine hepatitis virus (MHV-JHM), MHC class II was rapidly upregulated on microglia in the BN but not in the LEW strain. In the latter, inflammatory cells were the predominant MHC class II-expressing population. Nevertheless, most microglia in the LEW strain could, after some delay, be induced to express MHC class II after transfer of an experimental autoimmune encephalomyelitis (EAE)-inducing encephalitogenic T cell line. Paradoxically, strains resistant to EAE (exemplified by the BN) contained more constitutive MHC class II-expressing microglia than susceptible ones, when a variety of strains were examined. The results clearly establish that the normal CNS may contain MHC class II-expressing cells that are a resident rather than a transient blood-derived population. It is significant that this expression is strain related, but there is no evidence that microglial cell constitutive MHC class II expression predisposes to EAE susceptibility.
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PMID:Resident macrophages (ramified microglia) of the adult brown Norway rat central nervous system are constitutively major histocompatibility complex class II positive. 845 8

After intraperitoneal infection with mouse hepatitis virus, strain JHM (JHMV), JHMV replicated in the spleen of C57BL/6 mice for a few days but cleared within a week. The acute viral clearance coincided with moderate expansion of CD8+T cells and modest expansion of CD4+T cells, and was impaired moderately in mice depleted of CD8+T cells and completely in mice depleted of both CD4+ and CD8+T cell subsets. Flow cytometric analysis showed that expression of cell surface markers on the spleen T cells changed during JHMV infection. CD8+T cells expressing increased amounts of CD11a, CD43, CD44 and CD49d, and those expressing decreased levels of T cell receptor alpha beta, CD8, CD45RB and L-selectin were expanded in the spleen after JHMV infection. However, they did not express CD11b, CD25 or NK1.1. They used highly heterogenous V beta chains for their T cell receptors. In addition to CD11ahighCD8+T cells, CD11ahighCD4+T cells were detected transiently after JHMV infection. The virus-specific cytotoxic T lymphocyte (CTL) activity was observed in both CD4+ and CD8+ spleen T cells from mice 7 days post-infection. The present study shows the dynamics of CD8+ and CD4+T cells in the spleen during JHMV infection in mice and suggests that CD11ahighT cells may be involved in JHMV clearance in vivo because their appearance was temporally correlated with T cell-mediated viral clearance in vivo and antiviral CTL activity in vitro.
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PMID:Characterization of T cells expanded in vivo during primary mouse hepatitis virus infection in mice. 874 3

Interferon-alpha (IFN-alpha) therapy for hepatitis and malignant tumor frequently results in autoimmune thyroid disease (AITD); this fact indicates an association of IFN-alpha with autoimmunity. In order to study the mechanism, an investigation of the effects of human IFN-alpha on T cells, T cell subpopulations, B cells, macrophages and natural killer cells of patients with AITD and normal controls was carried out. It has been found that T cells were inhibited by IFN-alpha with dosage dependency, particularly the T suppressor (CD8/CD11b) in both the patients with AITD and normal controls. An increase in number of B cells and macrophages with stimulation of IFN-alpha was also found in both groups. The results suggest that the decrease of suppressive T cells and increase B cells and macrophages may be responsible for IFN-alpha induced autoimmunity.
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PMID:[Effects of human interferon-alpha on periphral blood mononuclear cells of the patients with autoimmune thyroid disease]. 938 11

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
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PMID:Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice. 971 10

Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium compound that activates the immune system. In this study, we investigated the action of propagermanium on T-cell-mediated murine hepatic injury induced by concanavalin A (Con A). Oral administration of propagermanium inhibited the development of liver injury about 10 h after ConA injection. Histological analysis demonstrated that propagermanium attenuated the extent of liver damage compared with controls, reducing infiltration by leucocytes, especially CD11b-positive cells. Infiltration by CD4-positive cells was not affected. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are crucial for the development of hepatitis in this model. Propagermanium treatment induced significant inhibition of subsequent TNF-alpha production about 10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-10, IL-4 and IL-12 production. This effect on TNF-production coincided with the inhibition of aminotransferase activity late in the progression of Con A-induced liver injury. These facts suggest that this compound affects the macrophages (Mphi) function in the liver sinusoid. Therefore, Mphi were cultured with liver sinusoidal endothelial cells (SEC) and the effect of propagermanium on TNF-alpha production in the presence of IFN-gamma was determined. TNF-alpha production was reduced significantly in the coculture of Mphi and SEC when Mphi was treated with propagermanium. These results might explain the mechanisms by which propagermanium inhibits Con-A-induced liver injury. That is, propagermanium improves hepatitis through mechanisms including the reduced production of TNF-alpha, without modification of Th1- and Th2-cell function.
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PMID:Protection against concanavalin A-induced murine liver injury by the organic germanium compound, propagermanium. 987 94

Activated cytotoxic T-cell-mediated hepatocyte apoptosis via Fas/Fas-ligand and perforin/granzyme pathways are believed to involve the model of concanavalin A (ConA)-induced hepatitis. The purpose of the present study is to investigate whether the cytokine response modifier A (crmA) gene effectively inhibits the hepatocyte apoptosis of ConA-induced hepatitis. We examined survival rates, liver pathology, immune histological changes, and cytokine profiles from mice receiving the recombinant adenovirus vectors containing cre and/or crmA genes, transferred to the liver 3 days before ConA injection, and a crmA gene nonexpression control group. Injection of ConA into mice rapidly led to massive hepatocyte apoptosis, and infiltration of leukocytes, especially CD11b(+) inflammatory cells. In contrast, liver damage was dramatically reduced in the mice that expressed the crmA gene. However, infiltration by CD4(+) cells was not affected. The survival of the mice increased significantly to 100% in the treated group versus the control group. Furthermore, we demonstrated that interleukin (IL)-18 plays an important role in ConA-induced hepatitis, and that crmA expression significantly inhibited IL-18 secretion. Our results showed that the crmA gene effectively inhibits apoptosis induced by ConA hepatitis. This indicates a potential therapeutic usage of crmA for protection from cellular damage due to hepatitis.
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PMID:CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis. 1293 45

Mouse hepatitis virus strain JHM (MHV-JHM) causes acute encephalitis and acute and chronic demyelinating diseases in mice. Dendritic cells (DCs) are key cells in the initiation of innate and adaptive immune responses, and infection of these cells could potentially contribute to a dysregulated immune response; consistent with this, recent results suggest that DCs are readily infected by another strain of mouse hepatitis virus, the A59 strain (MHV-A59). Herein, we show that the JHM strain also productively infected DCs. Moreover, mature DCs were at least 10 times more susceptible than immature DCs to infection with MHV-JHM. DC function was impaired after MHV-JHM infection, resulting in decreased stimulation of CD8 T cells in vitro. Preferential infection of mature DCs was not due to differential expression of the MHV-JHM receptor CEACAM-1a on mature or immature cells or to differences in apoptosis. Although we could not detect infected DCs in vivo, both CD8(+) and CD11b(+) splenic DCs were susceptible to infection with MHV-JHM directly ex vivo. This preferential infection of mature DCs may inhibit the development of an efficient immune response to the virus.
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PMID:Preferential infection of mature dendritic cells by mouse hepatitis virus strain JHM. 1647 57

Systemic exposure to bacterial lipopolysaccharide (LPS, endotoxin) induces hypotension, disseminated intravascular coagulation and neutrophil infiltration in various organs including the lung, kidney and liver. A rat endotoxemic neutrophilic hepatitis model (repeat dose LPS, 10 mg/kg, i.v. 24 hours apart) was developed exhibiting hepatic neutrophil infiltration and mid-zonal hepatic necrosis. The goal of the study was to investigate the role of the intracellular enzyme calpain in the development of neutrophilic hepatitis with midzonal necrosis in this model. A second goal was to compare the observed protective effects of calpain inhibition with a relatively selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) and an inhibitor of coagulation, heparin. When compared to rats administered LPS alone, administration of calpain 1 inhibitor prior to LPS significantly reduced hepatic iNOS expression, hepatic neutrophil infiltration and attenuated midzonal hepatic necrosis. Administration of AG or heparin prior to LPS also decreased liver iNOS expression, hepatic neutrophil infiltration and liver pathology comparable to calpain inhibition. Blood neutrophil activation, as measured by the neutrophil adhesion molecule CD11b integrin, was upregulated in all the LPS treated groups regardless of inhibitor administration. We conclude that amelioration of liver pathology via calpain inhibition is likely dependent on the down-regulation of iNOS expression in the rat model of LPS-mediated hepatitis.
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PMID:Calpain inhibition attenuates iNOS production and midzonal hepatic necrosis in a repeat dose model of endotoxemia in rats. 1716 36

Several studies have investigated the role of neutrophils during endotoxin-mediated liver injury, yet the precise mechanism for endotoxin-mediated hepatic neutrophil transmigration is unknown. The primary objective of this study was to establish a reliable lipopolysaccharide (LPS)-mediated necro-hepatitis model to investigate the mechanisms of hepatic neutrophil infiltration following LPS administration. Male Sprague Dawley rats were administered a single (5 or 10 mg kg(-1), i.v.) or repeated injection of LPS (10 mg kg(-1), i.v., 24 h apart) with appropriate controls (i.v. saline) and were killed at various time points following LPS injection. Significant hematologic changes included neutrophilia, elevation of the neutrophil to lymphocyte ratio and toxic changes in neutrophils. Biochemical changes were observed in several liver (aspartate aminotransferase AST, gamma glutamyl transferase GGT) and kidney (blood urea nitrogen BUN) associated parameters generally at the earliest time points. Histopathology revealed a time-dependent neutrophil and mononuclear infiltration around the periportal areas in the single dose study and multifocal midzonal coagulative necrosis in the repeated dose study. The neutrophil adhesion molecule, CD 11b was up-regulated in single and repeat dose studies. Based on these studies, a reliable LPS-mediated hepatitis model with necrosis was developed by intravenous administration of LPS in a repeat dose fashion. Midzonal hepatic necrosis, peripheral neutrophilia, hepatic neutrophil infiltration and up-regulation of CD11b were the most significant and consistent markers of LPS mediated effects in this model.
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PMID:Characterization of a lipopolysaccharide mediated neutrophilic hepatitis model in Sprague Dawley rats. 1737 Feb 40


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