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)

We characterize the specificity of a polyclonal antibody against heat shock protein 60 (hsp60) and present an application for ultrastructural localization studies of this protein. The antibody was obtained from an IgG fraction (AB 121) originally raised against the calcium binding protein calsequestrin by immunoabsorption on isolated rat liver hsp60. As shown by partial N-terminal amino acid sequence analysis of immunoprecipitated proteins AB 121 contained reactivities against hsp60, calsequestrin and the glycoprotein fetuin. In rat heart AB 121 recognized calsequestrin and hsp60. In human and rat liver the only reacting protein was hsp60. In rat erythrocytes the antibody bound to 61 kDa and 58 kDa isoforms of fetuin. According to published data no amino acid sequence homologies nor common motifs are found between calsequestrin, hsp60 and fetuin. As the first application the anti-hsp60 antibody was used for immuno-gold electron microscopical localization of hsp60: in myocardiocytes and hepatocytes of the rat strong labelling was obtained exclusively in mitochondria. No extramitochondrial structures were labelled. The specificity of the antibody and its ability to be visualized by immuno-gold electron microscopy offers the possibility to study the expression of this protein in the liver and in other organs. Possible clinical applications of these studies are discussed, since hsp60 could be a target antigen of autoantibodies in diseases such as autoimmune hepatitis, primary sclerosing cholangitis or primary biliary cirrhosis.
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PMID:Immuno-gold electron microscopical detection of heat shock protein 60 (hsp60) in mitochondria of rat hepatocytes and myocardiocytes. 751 75

Male A/JCr mice with naturally occurring Helicobacter hepaticus infection develop a progressive chronic active hepatitis and liver tumors, despite the presence of serum antibodies to Helicobacter proteins. A rabbit antiserum prepared against the bacterial proteins immunoreacted with hepatocytes present in liver sections from infected mice with progressive lesions. We found that sera from these mice contained IgG antibodies that reacted in immunoblots with recombinant heat shock protein 70 (DmaK from Escherichia coli) but not with heat shock protein 60 (GroEL) or heat shock protein 10 (GroES). A rabbit antibody to heat shock protein 70 reacted with H. hepaticus in tissue sections and to a H. hepaticus protein (70 kd) in Western blots. Immunohistochemistry and in situ hybridization for heat shock protein 70 revealed that individual hepatocytes and other cells expressed the protein in livers with hepatitis but not usually in normal livers. Liver tumors and preneoplastic lesions in infected mice did not usually express heat shock protein 70 except focally in a few tumors. In situ hybridization for H. hepaticus 16S rRNA showed that the bacteria was found throughout the liver associated with hepatitis but not within tumors. CD3+ T lymphocytes were found in close association with hepatic lesions. These data suggest a role for autoimmunity in progressive hepatitis and carcinogenesis in livers infected with H. hepaticus.
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PMID:Autoimmunity in chronic active Helicobacter hepatitis of mice. Serum antibodies and expression of heat shock protein 70 in liver. 857 13

The morphology of autoimmune hepatitis is characterized by portal-periportal predilection of necroinflammatory lesions. In comparison to the viral type of hepatitis severe piece-meal-necroses, the collapse of periportal parenchyma, and to a higher degree acinar transformation of hepatocytes are more prominent. The autoimmune hepatitis may start with acute disease displaying unusual clinical und histopathologic features. The postinfantile giant cell hepatitis seems to constitute a variant of autoimmune hepatitis. Autoimmune hepatitis has been reproduced in animal models and it could be demonstrated in rabbits that humoral immunity plays a role in tissue damage. The importance of cellular mechanisms could be analyzed in syngenic mice showing that the CD4-positive lymphocytes play a pivotal role. The most promising candidate antigen seems to be the asialoglycoprotein-receptors including the liver specific protein (LSP). By immunohistologic analysis dense deposits of IgG could be demonstrated in sinusoids and on the membranes of hepatocytes. In accordance with in vitro data the determination of CD4 positive lymphocytes in the tissue was found to play a decisive role in cellular immune reaction. The HSP65 molecule seems to evoke mechanisms that have been shown to play a pathogenetic role in experimental arthritis.
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PMID:[Autoimmune hepatitis]. 860 Jun 83

The antibody to 65 KD mycobacterial heat shock protein (HSP65) and antibody to human superoxide dismutase (H-SOD) were measured by ELISA in patients with autoimmune hepatitis (AIH), and results were compared with those of patients with chronic active hepatitis C (CAH-C) or systemic lupus erythematosus (SLE) and normal subjects (NS). Patients with AIH had significantly higher OD values of anti-HSP65 antibody and anti-H-SOD antibody compared with those of patients with CAH-C or SLE and NS. OD values of anti-HSP65 antibody were correlated with those of anti-SOD antibody. Affinity-purified anti-SOD antibody reacted with HSP65. Analysis of the amino acid sequence of human SOD showed that 7 segments, corresponding to r to 25 amino acid residues, exhibited 50 to 71% homology with that of my mycobacterial HSP65.
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PMID:Detection of antibodies to 65 KD heat shock protein and to human superoxide dismutase in autoimmune hepatitis-molecular mimicry between 65 KD heat shock protein and superoxide dismutase. 860 87

Understanding the function of the hepatitis B virus X protein (HBx) is fundamental to elucidating the underlying mechanisms of hepatitis and hepatocarcinogenesis caused by hepatitis B virus (HBV) infection. We identified heat shock protein 60 (Hsp60) as a novel cellular target of HBx by the combination of affinity purification and mass spectrometry. Physical interaction between HBx and Hsp60 was confirmed by standard immunoprecipitation and immunoblot methods. Analysis of HBx deletion constructs showed that amino acids 88-117 of HBx were responsible for the binding to Hsp60. Confocal laser microscopy demonstrated that HBx and Hsp60 colocalized in mitochondria. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL) revealed that the introduction of Hsp60 into cells facilitated HBx-induced apoptosis. These findings suggest the importance of the molecular chaperon protein Hsp60 to the function of HBV viral proteins.
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PMID:Interaction of the hepatitis B virus X protein (HBx) with heat shock protein 60 enhances HBx-mediated apoptosis. 1512 Jun 23

Extracellular heat shock protein 60 (HSP60) has been considered a proinflammatory danger signal. Yet, HSP60 can also down-regulate experimental immune arthritis and diabetes models by specific inhibition of Th1-like responses. We now report that HSP60 in vitro differentially modulates the expression of Th1/Th2 transcription factors in human T cells: HSP60 down-regulates T-bet, NF-kappaB, and NFATp and up-regulates GATA-3, leading to decreased secretion of TNF-alpha and IFN-gamma and enhanced secretion of IL-10. These effects depended on TLR2 signaling and could not be attributed to LPS or to other contaminants. In BALB/c mice, HSP60 in vivo inhibited the clinical, histological, and serological manifestations of Con A-induced hepatitis associated with up-regulated T cell expression of suppressor of cytokine signaling 3 and GATA-3 and down-regulated T-bet expression. These results provide a molecular explanation for the effects of HSP60 treatment on T cell inflammation via innate regulation of the inflammatory response.
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PMID:Heat shock protein 60 inhibits Th1-mediated hepatitis model via innate regulation of Th1/Th2 transcription factors and cytokines. 1574 53