Tyrosine kinase is essential for the constitutive expression of type I interleukin-1 receptor in human fibroblast cells.
The effect of genistein, an inhibitor of tyrosine kinase, on the constitutive expression of type I interleukin-1 receptor (IL-1RI) was examined in the human lung fibroblast cell line TIG-1, which has been shown to express only type I IL-1R. Genistein inhibited the 125I-labeled IL-1alpha binding to TIG-1 cells in both a time and dose dependent manner. Scatchard plot analysis revealed that the number of IL-1RI decreased with no change in binding affinity. Genistein did not affect the level of IL-1RI mRNA, and cycloheximide did not inhibit the down-regulatory effect of genistein. These results indicate that genistein inhibits IL-1RI expression, not at the transcriptional level, but at the post-translational level. IL-1RI expression, IL-1R associated kinase (IRAK) activity and IL-1-induced-IL-6 production were all down-regulated by pretreatment with genistein. These findings indicate that tyrosine kinase activity is essential for the constitutive expression of functional IL-1RI.
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, 467-8603 Japan.
T
T
Takii
A
A
Ito
S
S
Kawashima
A
A
Ninomiya
T
T
Matsumura
H
H
Hayashi
K
K
Onozaki
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D053573:Receptors, Interleukin-1 Type I; D011994:Recombinant Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D011994:Recombinant Proteins; D003513:Cycloheximide; D019833:Genistein; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D053592:Interleukin-1 Receptor-Associated Kinases