IFN-alpha and IL-12 induce IL-18 receptor gene expression in human NK and T cells.
IL-18 is a proinflammatory cytokine that enhances innate and specific Th1 immune responses. During microbial infections, IL-18 is produced by activated macrophages. IL-18 exerts its effects in synergy with IFN-alpha or IL-12 to induce IFN-gamma. Here we show that in human NK and T cells IFN-alpha and IL-12 strongly up-regulate mRNA expression of the IL-18R components, accessory protein-like (AcPL) and IL-1R-related protein (IL-1Rrp). In addition, IFN-alpha enhanced the expression of MyD88, an adaptor molecule involved in IL-18 signaling. Pretreatment of T cells with IFN-alpha or IL-12 enhanced IL-18-induced NF-kappaB activation and sensitized the cells to respond to lower concentrations of IL-18. AcPL and IL-1Rrp genes were strongly expressed in T cells polarized with IL-12, whereas in IL-4-polarized cells these genes were expressed at very low levels, indicating that AcPL and IL-1Rrp genes are preferentially expressed in Th1 cells. In conclusion, the results suggest that IFN-alpha and IL-12 enhance innate as well as Th1 immune response by inducing IL-18R expression.
Sareneva
T
T
Department of Virology, National Public Health Institute, Helsinki, Finland.
Julkunen
I
I
Matikainen
S
S
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic / Q000502:physiology; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000943:Antigens, Differentiation; C508572:IL18R1 protein, human; C115629:IL18RAP protein, human; D016898:Interferon-alpha; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma; D004247:DNA