title: Altered expression of SHIP, a Toll-like receptor pathway inhibitor, is associated with the severity of liver fibrosis in chronic hepatitis C virus infection.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Essen, Essen 45147, Germany.
authors.forename: Antonios
authors.initials: A
authors.lastname: Katsounas
authors.forename: Martin
authors.initials: M
authors.lastname: Trippler
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
mesh_terms: D001706:Biopsy; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D016014:Linear Models; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018832:Molecular Chaperones; D020411:Oligonucleotide Array Sequence Analysis; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases