The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains. 2004

Simon Hör, and Heide Pirzer, and Laure Dumoutier, and Finn Bauer, and Sabine Wittmann, and Heinrich Sticht, and Jean-Christophe Renauld, and René de Waal Malefyt, and Helmut Fickenscher
Virology Department, Ruprecht-Karls University, D-69120 Heidelberg, Germany, Cambridge Institute for Medical Research, Cambridge CB2 2XY, United Kingdom.

The cellular members of the interleukin-10 (IL-10) cytokine family share sequence homology with IL-10, whereas their sites of expression and their functions are divergent. One of these factors, AK155 or IL-26, was discovered because of its overexpression in human T lymphocytes after growth transformation by the simian rhadinovirus herpesvirus saimiri. In addition, the gene is transcribed in various types of primary and immortalized T-cells. Here we describe epithelial cells, namely colon carcinoma cells and keratinocytes, as targets of this T-cellular lymphokine. Purified recombinant IL-26 induced the rapid phosphorylation of the signal transducer and activator of transcription factors 1 and 3. As a result, secretion of IL-10 and IL-8, as well as cell surface expression of CD54 were enhanced. Moreover, we show that the IL-26 protein binds to heparin, is released from the cell surface, and can be functionally inhibited by heparin. The sensitivity to recombinant IL-26 of various cell lines strictly correlated with the expression of the long chain of the IL-20 receptor. Because blocking antibodies against either the short chain of the IL-10 receptor or the long chain of the IL-20 receptor inhibited IL-26-dependent signal transduction, and transient expression of these receptor chains induced IL-26 responsivity in non-sensitive cells, we propose that the IL-20 receptor 1 and IL-10 receptor 2 chains participate in forming the IL-26 receptor. Targeting epithelial cells, the T-cell lymphokine IL-26 is likely to play a role in local mechanisms of mucosal and cutaneous immunity.

UI MeSH Term Description Entries
D007378 Interleukins Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. Interleukin
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell

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