The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains.
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.
Hör
Simon
S
Virology Department, Ruprecht-Karls University, D-69120 Heidelberg, Germany, Cambridge Institute for Medical Research, Cambridge CB2 2XY, United Kingdom.
Pirzer
Heide
H
Dumoutier
Laure
L
Bauer
Finn
F
Wittmann
Sabine
S
Sticht
Heinrich
H
Renauld
Jean-Christophe
JC
de Waal Malefyt
René
R
Fickenscher
Helmut
H
D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular; D002462:Cell Membrane / Q000378:metabolism; D003110:Colonic Neoplasms; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects*; D006367:HeLa Cells; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D018123:Receptors, Interleukin / Q000502:physiology*; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C406767:IL26 protein, human; D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C492510:interleukin-20 receptor; D006493:Heparin