ID | 32294 |
JaLCDOI | |
FullText URL | |
Author |
Kuinose, Masahiko
Iwagaki, Hiromi
Morimoto, Yoshinori
Kohka, Hideo
Kobashi, Kenta
Inagaki, Masaru
Urushihara, Naoto
Tanaka, Noriaki
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Abstract | Tacrolimus (FK-506) and cyclosporin A (CsA) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on the production of interleukin-18 (IL-18) remains undefined. We have examined the effects of FK-506 and CsA on the cytokine generation of human peripheral blood mononuclear cells (PBMCs) in mixed lymphocyte reaction (MLR) with lipopolysaccharide (LPS). We studied the levels of interleukin-18 (IL-18), IL-12, IL-10, IL-6, IL-2 and interferon-gamma (IFN-gamma) in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-gamma, IL-2, IL-6, IL-10 and IL-12 were detected 12 h after MLR and markedly increased thereafter. In contrast, production of IL-18 was detected at 12 h, reached a near maximum level at 24 h and decreased at 72 h. These results suggested that IFN-gamma production depended on IL-18, IL-12 and IL-2 in the early phase of MLR and depended mainly on IL-12 and IL-2 in the late phase. Both calcineurin antagonists inhibit the generation of IL-18, which plays a large role in allogeneic cell interactions, in macrophages and they also promote an equivalent down-regulation of T helper 1 (Th1) and Th2 responses in a concentration-dependent manner. About 90% of IFN-gamma production induced by MLR was inhibited by an anti-IL-18 antibody, showing that IL-18 can trigger IFN-gamma production in MLR. These results suggest that dual signaling consisting of antigen-driven nuclear factor of activated T cells (NFAT) activation and LPS-mediated NF-kappaB activation is crucial for IL-18 production in macrophages, and that IL-18 can trigger IFN-gamma production in T-cells by MLR. |
Keywords | tacrolimus
cyclosporin
calcineurin antagonist
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Amo Type | Article
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Publication Title |
Acta Medica Okayama
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Published Date | 2000-10
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Volume | volume54
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Issue | issue5
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Publisher | Okayama University Medical School
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Start Page | 201
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End Page | 209
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ISSN | 0386-300X
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NCID | AA00508441
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Content Type |
Journal Article
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language |
English
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File Version | publisher
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Refereed |
True
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PubMed ID | |
Web of Science KeyUT |