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)

Viral infection and type I interferon have been implicated in the pathogenesis of biliary atresia (BA), but the expression of toll-like receptors (TLRs) that recognize viruses, as well as of type 1 interferon specific signaling molecules are still unknown in BA. Fresh liver tissues were obtained from patients in early and late stage of BA and from patients with choledochal cyst (CC), as well as from normal controls receiving liver resection for benign lesion other than cholestasis or fibrosis. Archived liver tissues from patients with neonatal hepatitis (NH) were obtained for immunohistochemical studies. TLR2, 3, 4, 7 and 9 that recognized Gram-positive bacteria, double-stranded RNA virus, lipopolysaccharide, single-stranded RNA virus and DNA virus, respectively, were studied. Real-time quantitative reverse transcription polymerase chain reaction (QRT-PCR) was used to quantitate TLR, type I interferon specific molecule MxA, interleukin-6 (IL-6) and IL-8 mRNA expression and immunohistochemistry for TLR 7 and MxA protein staining. These results show that there were significantly higher TLR7 and lower TLR3 and TLR9 mRNA expression in early stage of BA than in CC. MxA mRNA expression was also significantly higher in early stage of BA and in CC than in late stage of BA. Immunoreactive TLR7 and MxA staining was higher in early stage of BA than in late stage of BA, NH and CC, which was associated with significantly higher IL-8 mRNA expression in BA than in CC. The results implicate involvement of TLRs, particularly TLR7, and type 1 specific interferon signaling in the pathogenesis of BA, especially in early stage, which is associated with upregulation of inflammatory cytokines IL-8.
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PMID:Expression of toll-like receptors and type 1 interferon specific protein MxA in biliary atresia. 1707 76

Co-infection and superinfection of hepatitis B virus (HBV) with hepatitis delta virus (HDV) leads to suppression of HBV replication both in patients and in animal and cellular models. The mechanisms behind this inhibition have not previously been explored fully. HBV replication is governed by four promoters and two enhancers, Enh1 and Enh2. Repression of these enhancers has been reported to be one of the main mechanisms of HBV inhibition. Moreover, in a previous study, it has been demonstrated that alpha interferon (IFN-alpha)-inducible MxA protein inhibits HBV replication. HDV encodes two proteins, p24 and p27. p27 was shown to activate several heterologous promoters, including HBV promoters. In an attempt to analyse the mechanisms of HBV inhibition by HDV, the question was raised whether HDV proteins could act directly by repressing HBV enhancers, and/or indirectly by activating the MxA gene. This issue was addressed in a co-transfection model in Huh-7 cells, using p24- or p27-expressing plasmids along with Enh1, Enh2, HBV and MxA promoter-luciferase constructs. Enh1 and Enh2 were strongly repressed, by 60 and 80 % and 40 and 60 %, by p24 and p27, respectively. In addition, p27 was responsible for threefold activation of the MxA promoter and potentiation of IFN-alpha on this promoter. MxA mRNA quantification and a virus yield reduction assay confirmed these results. In conclusion, this study shows that HDV proteins inhibit HBV replication by trans-repressing its enhancers and by trans-activating the IFN-alpha-inducible MxA gene.
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PMID:Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene. 1962 66