Abstract
Hepatitis C-related fibrogenesis has been shown to involve complex interactions between peripheral and hepatic immune responses. Peripheral whole blood (PB) samples from patients with chronic hepatitis C (n = 36) were subjected to microarray analysis in order to identify gene expression patterns associated with immune pathways in PB and hepatic fibrosis. Distinct regulation of gene expression of inositol polyphosphate-5-phosphatase/145kDa (INPP5D or SHIP), a TLR2/TLR4-inhibitor, and heat shock protein 8/22 kDa (HSPB8), an endogenous TLR4-ligand, during fibrogenesis was identified and could be confirmed by quantitative reverse-transcription polymerase chain reaction. These results suggest a potential link between peripheral activity of the TLR4-pathway, peripheral SHIP-dependent immune regulation, and liver fibrosis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Biopsy
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Gene Expression Regulation
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Heat-Shock Proteins / biosynthesis*
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Heat-Shock Proteins / genetics
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Hepacivirus / physiology*
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Hepatitis C, Chronic / genetics
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Hepatitis C, Chronic / metabolism*
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Hepatitis C, Chronic / virology
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Humans
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Inositol Polyphosphate 5-Phosphatases
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Linear Models
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Liver Cirrhosis / genetics
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Liver Cirrhosis / metabolism*
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Liver Cirrhosis / virology
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Molecular Chaperones
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Oligonucleotide Array Sequence Analysis
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
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Phosphoric Monoester Hydrolases / biosynthesis*
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Phosphoric Monoester Hydrolases / genetics
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Protein Serine-Threonine Kinases / biosynthesis*
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Protein Serine-Threonine Kinases / genetics
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RNA / chemistry
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RNA / genetics
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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HSPB8 protein, human
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Heat-Shock Proteins
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Molecular Chaperones
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RNA
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Protein Serine-Threonine Kinases
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Phosphoric Monoester Hydrolases
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Inositol Polyphosphate 5-Phosphatases
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INPP5D protein, human
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases