Interferon-gamma mediates gene expression of IL-18 binding protein in nonleukocytic cells.
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.
Mühl
H
H
Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany. H.Muehl@em.unifrankfurt.de
Kämpfer
H
H
Bosmann
M
M
Frank
S
S
Radeke
H
H
Pfeilschifter
J
J
D002460:Cell Line; D002478:Cells, Cultured; D003110:Colonic Neoplasms; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D020382:Interleukin-18 / Q000235:genetics; D015603:Keratinocytes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D020382:Interleukin-18; C118370:interleukin-18 binding protein; D007371:Interferon-gamma