Coyle P, Philcox J C, Rofe A M
Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, Australia.
J Nutr. 1993 Sep;123(9):1464-70. doi: 10.1093/jn/123.9.1464.
The regulation of metallothionein induction in cultured rat hepatocytes was investigated with Zn, hormones, cytokines and either the synthetic glucocorticoid, dexamethasone, or the endogenous rat glucocorticoid, corticosterone. A concentration-dependent increase was seen with Zn (two- to fivefold increase in 24 h, Zn 10-50 mumol/L). Dexamethasone at 1 mumol/L increased metallothionein synthesis by fourfold that of the controls. Maximal metallothionein concentrations of 17-fold the control value were seen with 50 mumol/L Zn and 1 mumol/L dexamethasone. Interleukin-6 (1 x 10(5) U/L) alone did not induce metallothionein but increased it 35-65% with Zn+dexamethasone. Like dexamethasone, corticosterone had a dose dependent effect on metallothionein and synergy with Zn and Zn+interleukin-6. Dexamethasone was approximately 100 times more potent than corticosterone at 10-100 mumol/L. Physiological concentrations of corticosterone (1 mumol/L) when added alone, with Zn (10 mumol/L), and with Zn+interleukin-6 resulted in inductions of 2.2, 5.0 and 7.4-fold above the control cultures. Glucagon (1 mumol/L) had no independent effect but increased metallothionein by 31% and 33% with Zn(10 mumol/L)+dexamethasone (1 mumol/L) and Zn-dexamethasone+interleukin-6, respectively. There was no accumulation of metallothionein with interleukin-1 beta, tumor necrosis factor alpha or interferon gamma (1 x 10(5) U/L) alone, but interleukin-1 beta and tumor necrosis factor alpha enhanced the response obtained with Zn+dexamethasone with and without interleukin-6. Insulin (100 U/L) alone, caused metallothionein accumulation and further enhanced the response seen with Zn+dexamethasone+interleukin-6+glucagon. No additional enhancement was seen with interleukin 1 beta+tumor necrosis factor alpha+interferon. The results demonstrate that concentrations of corticosterone in rats with experimental inflammation facilitate metallothionein induction with Zn and interleukin-6.(ABSTRACT TRUNCATED AT 250 WORDS)
利用锌、激素、细胞因子以及合成糖皮质激素地塞米松或内源性大鼠糖皮质激素皮质酮，研究了培养的大鼠肝细胞中金属硫蛋白诱导的调控情况。锌呈现出浓度依赖性增加（24小时内增加2至5倍，锌浓度为10 - 50 μmol/L）。1 μmol/L的地塞米松使金属硫蛋白合成增加至对照的四倍。50 μmol/L锌和1 μmol/L地塞米松时，金属硫蛋白浓度达到对照值的17倍。单独的白细胞介素-6（1×10⁵ U/L）不诱导金属硫蛋白，但与锌+地塞米松一起时使其增加35 - 65%。与地塞米松一样，皮质酮对金属硫蛋白有剂量依赖性作用，并与锌以及锌+白细胞介素-6协同作用。在10 - 100 μmol/L时，地塞米松的效力约为皮质酮的100倍。单独添加生理浓度的皮质酮（1 μmol/L）、与锌（10 μmol/L）以及与锌+白细胞介素-6一起时，诱导水平分别比对照培养物高2.2倍、5.0倍和7.4倍。胰高血糖素（1 μmol/L）无独立作用，但与锌（10 μmol/L）+地塞米松（1 μmol/L）以及锌-地塞米松+白细胞介素-6一起时分别使金属硫蛋白增加31%和33%。单独使用白细胞介素-1β、肿瘤坏死因子α或干扰素γ（1×10⁵ U/L）时金属硫蛋白无积累，但白细胞介素-1β和肿瘤坏死因子α在有或无白细胞介素-6的情况下增强了锌+地塞米松所产生的反应。胰岛素（100 U/L）单独作用时导致金属硫蛋白积累，并进一步增强了锌+地塞米松+白细胞介素-6+胰高血糖素所产生的反应。白细胞介素-1β+肿瘤坏死因子α+干扰素未产生额外增强作用。结果表明，实验性炎症大鼠体内的皮质酮浓度促进了锌和白细胞介素-6诱导金属硫蛋白。（摘要截断于250字）
