Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor

Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10144-9. doi: 10.1073/pnas.170291697.

Abstract

IL-10-related T cell-derived inducible factor (IL-TIF or IL-21) is a new cytokine structurally related to IL-10 and originally identified in the mouse as a gene induced by IL-9 in T cells and mast cells. Here, we report the cloning of the human IL-TIF cDNA, which shares 79% amino acid identity with mouse IL-TIF and 25% identity with human IL-10. Recombinant human IL-TIF was found to activate signal transducer and activator of transcription factors-1 and -3 in several hepatoma cell lines. IL-TIF stimulation of HepG2 human hepatoma cells up-regulated the production of acute phase reactants such as serum amyloid A, alpha1-antichymotrypsin, and haptoglobin. Although IL-10 and IL-TIF have distinct activities, antibodies directed against the beta chain of the IL-10 receptor blocked the induction of acute phase reactants by IL-TIF, indicating that this chain is a common component of the IL-10 and IL-TIF receptors. Similar acute phase reactant induction was observed in mouse liver upon IL-TIF injection, and IL-TIF expression was found to be rapidly increased after lipopolysaccharide (LPS) injection, suggesting that this cytokine contributes to the inflammatory response in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Amino Acid Sequence
  • Animals
  • Carcinoma, Hepatocellular
  • Cell Line
  • Cells, Cultured
  • Cloning, Molecular
  • Cytokines / chemistry
  • Cytokines / genetics
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • DNA, Complementary
  • Escherichia coli
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-10 / immunology
  • Liver Neoplasms
  • Mice
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured

Substances

  • Acute-Phase Proteins
  • Cytokines
  • DNA, Complementary
  • IL-10-related T cell-derived inducible factor, IL-TIF
  • Recombinant Proteins
  • Trans-Activators
  • Interleukin-10

Associated data

  • GENBANK/AJ277247