Human IL-19 regulates immunity through auto-induction of IL-19 and production of IL-10.
IL-19 is a novel, recently identified member of the IL-10 family of cytokines. We identified IL-10 as a cytokine that was strongly induced in IL-19-stimulated PBMC. IL-19-induced IL-10 secretion was dose-dependent and could be detected in culture supernatants after 3 h of stimulation. Furthermore, quantitative RT-PCR analysis demonstrated that IL-19 stimulation increased the level of IL-10 mRNA present within cells, suggesting that IL-19 is a transcriptional activator of IL-10. IL-19 was also able to induce its own expression, with IL-10 potently down-regulating this IL-19 'auto-induction'. LPS induction of IL-19 expression was also regulated by IL-10, demonstrating that IL-10 is likely an important regulator of human IL-19 induction. Maturation of dendritic cells from human PBMC in the presence of IL-19 resulted in an increase in IL-10 levels within these cells, whereas IL-12 was not affected. These results advance our understanding of the function of this novel cytokine and its regulation within the human immune system, in addition to providing a new insight into the control of the important immunoregulatory cytokine, IL-10.
Jordan
William J
WJ
Department of Oral Biology, University of Medicine and Dentistry of New Jersey, Newark, USA.
Eskdale
Joyce
J
Boniotto
Michele
M
Lennon
Greig P
GP
Peat
Jon
J
Campbell
John D M
JD
Gallagher
Grant
G
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D007378:Interleukins; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
C421250:IL19 protein, human; D007378:Interleukins; D016753:Interleukin-10