Takii T, Ito A, Kawashima S, Ninomiya A, Matsumura T, Hayashi H, Onozaki K
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, 467-8603 Japan.
Eur Cytokine Netw. 1999 Jun;10(2):237-46.
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.
在已被证明仅表达I型白细胞介素-1受体（IL-1RI）的人肺成纤维细胞系TIG-1中，研究了酪氨酸激酶抑制剂染料木黄酮对I型白细胞介素-1受体组成型表达的影响。染料木黄酮以时间和剂量依赖性方式抑制125I标记的IL-1α与TIG-1细胞的结合。Scatchard图分析显示IL-1RI的数量减少，而结合亲和力没有变化。染料木黄酮不影响IL-1RI mRNA的水平，环己酰亚胺也不抑制染料木黄酮的下调作用。这些结果表明，染料木黄酮抑制IL-1RI的表达，不是在转录水平，而是在翻译后水平。用染料木黄酮预处理可下调IL-1RI表达、IL-1受体相关激酶（IRAK）活性和IL-1诱导的IL-6产生。这些发现表明酪氨酸激酶活性对于功能性IL-1RI的组成型表达至关重要。
