Interferon-gamma mediates gene expression of IL-18 binding protein in nonleukocytic cells |
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Authors: | Mühl H Kämpfer H Bosmann M Frank S Radeke H Pfeilschifter J |
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Institution: | Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universit?t Frankfurt am Main, Frankfurt am Main, Germany. H.Muehl@em.unifrankfurt.de |
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Abstract: | Interleukin-18 (IL-18) binding protein is a soluble decoy receptor for IL-18 which efficiently antagonizes biological functions of IL-18 in vitro and in vivo. Since regulation of IL-18 activity likely contributes to the pathogenesis of inflammatory diseases as well as malignancies, we investigated gene expression of IL-18 binding protein (IL-18BP) in different human cell systems, namely in the keratinocyte cell line HaCaT, in the colon carcinoma cell line DLD-1, and in primary renal mesangial cells. In unstimulated cells only minute amounts of mRNA coding for IL-18 binding protein were detectable. However, in all three cell types gene expression was markedly upregulated by interferon-gamma (IFN-gamma). IL-18 is recognized as a pivotal mediator of IFN-gamma production. Therefore, the present data imply that activity of IL-18 is modulated by a negative feedback mechanism which is mediated by IFN-gamma-induced IL-18 binding protein. |
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