Altered expression of SHIP, a Toll-like receptor pathway inhibitor, is associated with the severity of liver fibrosis in chronic hepatitis C virus infection

J Infect Dis. 2011 Oct 15;204(8):1181-5. doi: 10.1093/infdis/jir500.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Gene Expression Regulation
  • Heat-Shock Proteins / biosynthesis*
  • Heat-Shock Proteins / genetics
  • Hepacivirus / physiology*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / virology
  • Humans
  • Inositol Polyphosphate 5-Phosphatases
  • Linear Models
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / virology
  • Molecular Chaperones
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoric Monoester Hydrolases / biosynthesis*
  • Phosphoric Monoester Hydrolases / genetics
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases / genetics
  • RNA / chemistry
  • RNA / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • HSPB8 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • RNA
  • Protein Serine-Threonine Kinases
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases
  • INPP5D protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases