Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor.
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.
Dumoutier
L
L
Ludwig Institute for Cancer Research, Brussels Branch and the Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Avenue Hippocrate 74, B1200-Brussels, Belgium.
Van Roost
E
E
Colau
D
D
Renauld
J C
JC
D000209:Acute-Phase Proteins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D018076:DNA, Complementary; D004926:Escherichia coli; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D008113:Liver Neoplasms; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D016207:Cytokines; D018076:DNA, Complementary; C404815:IL-10-related T cell-derived inducible factor, IL-TIF; D011994:Recombinant Proteins; D015534:Trans-Activators; D016753:Interleukin-10