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

Infection of C57BL/6 mice with the V5A13.1 strain of mouse hepatitis virus (MHV-V5A13.1) results in an acute encephalomyelitis and chronic demyelinating disease with features similar to the human demyelinating disease multiple sclerosis. Chemokines are a family of proinflammatory cytokines associated with inflammatory pathology in various diseases. The kinetics and histologic localization of chemokine production in the central nervous system of MHV-infected mice were examined to identify chemokines that contribute to inflammation and demyelination. Transcripts for the chemokines cytokine-response gene-2 (CRG-2), regulated on activation, normal T cell expressed and secreted (RANTES), macrophage-chemoattractant protein-1 and protein-3 (MCP-1, MCP-3), macrophage-inflammatory protein-1beta (MIP-1beta), and MIP-2 were detected in the brains of MHV-infected mice at 3 days postinfection (p.i.), and these transcripts were increased markedly in brains and spinal cords at day 7 p.i., which coincides with the occurrence of acute viral encephalomyelitis. By day 35 p.i., RANTES, CRG-2, and MIP-1beta were detected in brains and spinal cords of mice with chronic demyelination. CRG-2 mRNA expression colocalized with viral RNA and was associated with demyelinating lesions. Astrocytes were the predominant cell type expressing CRG-2 mRNA. These observations suggest a role for chemokines, notably CRG-2, in the initiation and maintenance of an inflammatory response following infection with MHV, which is important in contributing to demyelination.
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PMID:Dynamic regulation of alpha- and beta-chemokine expression in the central nervous system during mouse hepatitis virus-induced demyelinating disease. 955 36

Intracerebral infection of mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a chronic demyelinating disease with clinical and histological similarities with the human demyelinating disease multiple sclerosis (MS). Following MHV infection, chemokines including CXC chemokine ligand (CXCL)10 (IFN inducible protein 10 kDa), CXCL9 (monokine induced by IFN-gamma), and CC chemokine ligand 5 (RANTES) are expressed during both acute and chronic stages of disease suggesting a role for these molecules in disease exacerbation. Previous studies have shown that during the acute phase of infection, T lymphocytes are recruited into the CNS by the chemokines CXCL10 and CXCL9. In the present study, MHV-infected mice with established demyelination were treated with antisera against these two chemokines, and disease severity was assessed. Treatment with anti-CXCL10 reduced CD4+ T lymphocyte and macrophage invasion, diminished expression of IFN-gamma and CC chemokine ligand 5, inhibited progression of demyelination, and increased remyelination. Anti-CXCL10 treatment also resulted in an impediment of clinical disease progression that was characterized by a dramatic improvement in neurological function. Treatment with antisera against CXCL9 was without effect, demonstrating a critical role for CXCL10 in inflammatory demyelination in this model. These findings document a novel therapeutic strategy using Ab-mediated neutralization of a key chemokine as a possible treatment for chronic human inflammatory demyelinating diseases such as MS.
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PMID:Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurological function in a viral model of multiple sclerosis. 1156 31

HBV and HCV infections are associated with the increased production of reactive oxygen species (ROS) within the liver that are responsible for the oxidation of intracellular molecules and activation transcription factors. The aim of the present study was to establish whether the presence of hepatitis could be implicated in the elevation of oxidative stress (SOX) and plasma proinflammatory and chemoattractant cytokine levels in uraemic patients. The markers of SOX-autoantibodies to oxidized LDL (OxLDL-Ab); total peroxides; and the major antioxidant enzyme Cu/Zn superoxide dismutase (Cu/Zn SOD); as well as tumor necrosis factor-alpha (TNF-alpha); regulated upon activation, normal T cell expressed and secreted (RANTES); and macrophage inflammatory protein-1alpha (MIP-1alpha) and beta (MIP-1beta) levels were measured in the plasma of uraemic patients with hepatitis in comparison to subjects without hepatitis and to healthy volunteers. The values of total peroxide, Cu/Zn SOD, TNF-alpha, and MIP-1beta, were significantly elevated in uraemic patients when compared to the controls, whereas RANTES were decreased. MIP-1alpha and OxLDL-Ab were similar in the two groups. Cu/Zn SOD, MIP-1beta and RANTES concentrations were significantly higher in the hepatitis-positive relative to the hepatitis-negative group. Both MIP-1beta and RANTES were directly associated with Cu/Zn SOD levels and the presence of hepatitis. Multiple stepwise regression analysis has shown that the duration of dialysis, followed by the presence of hepatitis, independently and significantly predicted increased Cu/Zn SOD levels, whereas elevated Cu/Zn SOD as an independent variable was significantly associated with both increased both MIP-1beta and RANTES in uraemic patients. These results suggest that the presence of viral hepatitis status and liver injury are novel determinants of increased oxidative stress, as well as of increased MIP-1beta and RANTES levels in uraemic patients.
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PMID:Hepatitis intensified oxidative stress, MIP-1beta and RANTES plasma levels in uraemic patients. 1556 48