Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic / physiology
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / genetics
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Cell Line
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Cell Polarity / immunology
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Cells, Cultured
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DNA / metabolism
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Drug Synergism
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Gene Expression Regulation / immunology*
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Humans
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Interferon-alpha / physiology*
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Interferon-gamma / biosynthesis
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Interferon-gamma / genetics
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Interleukin-12 / physiology*
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Interleukin-18 / physiology
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Interleukin-18 Receptor alpha Subunit
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Interleukin-18 Receptor beta Subunit
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism*
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Lymphocyte Activation / immunology
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Myeloid Differentiation Factor 88
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NF-kappa B / metabolism
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Protein Binding / immunology
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Protein Biosynthesis
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Proteins / genetics
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RNA, Messenger / biosynthesis
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Receptors, Immunologic*
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Receptors, Interleukin / biosynthesis*
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Receptors, Interleukin / genetics*
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Receptors, Interleukin-1 / biosynthesis
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Receptors, Interleukin-1 / genetics
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Receptors, Interleukin-12
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Receptors, Interleukin-18
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic
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Antigens, Differentiation
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IL18R1 protein, human
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IL18RAP protein, human
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Interferon-alpha
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Interleukin-18
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Interleukin-18 Receptor alpha Subunit
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Interleukin-18 Receptor beta Subunit
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MYD88 protein, human
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Myeloid Differentiation Factor 88
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NF-kappa B
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Proteins
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RNA, Messenger
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Receptors, Immunologic
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Receptors, Interleukin
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Receptors, Interleukin-1
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Receptors, Interleukin-12
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Receptors, Interleukin-18
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Interleukin-12
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Interferon-gamma
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DNA