Effect of interleukin-6 neutralization on CYP3A11 and metallothionein-1/2 expressions in arthritic mouse liver
Effect of interleukin-6 neutralization on CYP3A11 and metallothionein-1/2 expressions in arthritic mouse liver
复制标题
DOI：
10.1016/j.ejphar.2006.11.072
复制
发表时间：
2007-03-06
影响因子：
5
通讯作者：
Yoshida, Takemi
中科院分区：
文献类型：
--
作者：
Ashino, Takashi;Arima, Yoshiko;Yoshida, Takemi
类风湿性关节炎的特征是滑膜组织的慢性炎症。我们使用类风湿性关节炎模型小鼠、人类 T 细胞白血病病毒 I 型 (HTLV-I) 转基因小鼠，研究了白细胞介素 (IL)-6 中和对慢性期炎症性疾病期间细胞色素 P450 或金属硫蛋白-1/2（金属硫蛋白）表达的影响。患有关节炎的HTLV-1转基因小鼠的血清IL-6浓度为129.9+/-26.1pg/ml。此外，在关节炎 HTLV-1 转基因小鼠肝脏中观察到信号转导子和转录激活子 (STAT) 1/3 磷酸化。与 CYP2C29 或 CYP2E1 mRNA 相比，HTLV-1 转基因小鼠肝脏中关节炎的发生更强烈地减少了 CYP3A1 I mRNA。 CYP3A 蛋白和睾酮 6-羟基化活性也以与相应 CYP3A11 mRNA 水平类似的方式发生变化。另一方面，与野生型或非关节炎小鼠相比，金属硫蛋白mRNA被显着诱导。在治疗后48小时，通过IL-6抗体，在发育的关节炎小鼠中观察到的CYP3A抑制和金属硫蛋白mRNA过表达活性恢复到非关节炎HTLV-1转基因小鼠的基因状况。本研究揭示，在关节炎HTLV-1转基因小鼠中，CYP3A11和金属硫蛋白的表达受到关节炎及其体循环释放IL-6的影响，并且通过CYP3A 11 mRNA的下调和金属硫蛋白mRNA的诱导恢复IL-6的中和。 (c) 2006 Elsevier B.V. 保留所有权利。
Rheumatoid arthritis is characterized by chronic inflammation of the synovial tissue. We examined the effect of interleukin (IL)-6 neutralization on the expression of cytochrome P450 ormetallothioncin-1/2 (metallothionein) during chronic phase inflammatory disease using rheumatoid arthritis model mice, human T-cell leukemia virus type I (HTLV-I) transgenic mice. Serum IL-6 concentrations of arthritis-developed HTLV-1 transgenic mice were 129.9 +/- 26.1 pg/ml. Moreover, signal transducer and activator of transcription (STAT) 1/3 phosphorylations was observed in arthritic HTLV-1 transgenic mouse livers. CYP3A1 I mRNA was more strongly reduced by the development of arthritis in HTLV-1 transgenic mouse livers as compared with CYP2C29 or CYP2E1 mRNAs. CYP3A protein and testosterone 6 -hydroxylation activity also changed in a similar manner to the corresponding CYP3A11 mRNA level. On the other hand, metallothionein mRNA was significantly induced as compared with that of wild-type or non-arthritic mice. CYP3A suppression and metallothionein mRNA overexpression activity seen in the developed arthritic mice returned to the gene conditions of the non-arthritic HTLV-1 transgenic mice by IL-6 antibody at 48 h after treatment. The present study has revealed that CYP3A11 and metallothionein expressions are affected by the release of IL-6 by arthritis and its systemic circulation, and neutralization of IL-6 recovered from the down-regulation of CYP3A 11 mRNA and the induction of metallothionein mRNA in arthritic HTLV-1 transgenic mice. (c) 2006 Elsevier B.V. All rights reserved.