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

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.

• Authors: L Dumoutier, E Van Roost, D Colau, J C Renauld
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 97 Issue 18 Pg. 10144-9 (Aug 29 2000) ISSN: 0027-8424 [Print] United States
• PMID: 10954742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Acute-Phase Proteins (genetics)
• Amino Acid Sequence
• Animals
• Carcinoma, Hepatocellular
• Cell Line
• Cells, Cultured
• Cloning, Molecular
• Cytokines (chemistry, genetics, pharmacology, 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, pharmacology)
• Sequence Alignment
• Sequence Homology, Amino Acid
• Signal Transduction
• T-Lymphocytes (immunology)
• Trans-Activators (metabolism)
• Tumor Cells, Cultured