Suh Han Na, Lee Yu Jin, Han Ho Jae
Department of Veterinary Physiology, Biotherapy Human Resources Center (BK21), College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea.
J Cell Physiol. 2009 Mar;218(3):643-52. doi: 10.1002/jcp.21641.
Interleukin-6 (IL-6) is involved in a variety of biological responses, including the glucose metabolism and cell growth, which is a critical physiological function requiring multiple metabolic pathways. Therefore, in the present study, we examined the effect of IL-6 on 2-deoxyglucose (2-DG) uptake and the related signaling pathways in primary cultured chicken hepatocytes. IL-6 increased 2-DG uptake in a time- (> or =4 h) and a dose -(> or =5 ng/ml) dependent manner. Indeed, IL-6 increased GLUT-2 mRNA and protein expression as well as 2-DG uptake, which were blocked by actinomycin D (AD, transcription inhibitor) and cycloheximide (CHX, translation inhibitor). IL-6 (10 ng/ml) increased the level of IL-6Ralpha and glycoprotein (gp) 130 (IL-6Rbeta) protein expressions. IL-6 increased Janus Kinase (JAK)-2, signal transducer and activator of transcription (STAT)-3 phosphorylation, intracellular Ca(2+) concentration, and PKC phosphorylation. IL-6-induced increase of 2-DG uptake and GLUT-2 protein expression were blocked by JAK2-specific siRNA, a STAT3 inhibitor, staurosporine, and bisindolylmaleimide I (PKC inhibitors). In addition, IL-6 increased EGFR/src/FAK, PI3K/Akt phosphorylation and 2-DG uptake as well as GLUT-2 protein expression, which were blocked by AG 1478 (EGF receptor inhibitor), PP2 (src family of tyrosine kinase inhibitor), PI3K-specific siRNA, and a Akt inhibitor. Furthermore, IL-6 increased p44/42 MAPKs phosphorylation and p44 and p42 MAPK-specific siRNA mixture blocked IL-6-induced increase of 2-DG uptake and GLUT-2 protein expression. In conclusion, IL-6 stimulates the 2-DG uptake through p44/42 MAPKs activation via Ca(2+)/PKC and EGF receptor in primary cultured chicken hepatocytes.
白细胞介素-6（IL-6）参与多种生物学反应，包括葡萄糖代谢和细胞生长，这是一种需要多种代谢途径的关键生理功能。因此，在本研究中，我们检测了IL-6对原代培养鸡肝细胞中2-脱氧葡萄糖（2-DG）摄取及相关信号通路的影响。IL-6以时间（≥4小时）和剂量（≥5 ng/ml）依赖性方式增加2-DG摄取。实际上，IL-6增加了葡萄糖转运蛋白2（GLUT-2）的mRNA和蛋白表达以及2-DG摄取，而放线菌素D（AD，转录抑制剂）和环己酰亚胺（CHX，翻译抑制剂）可阻断这些作用。IL-6（10 ng/ml）增加了IL-6Rα和糖蛋白（gp）130（IL-6Rβ）蛋白表达水平。IL-6增加了Janus激酶（JAK）-2、信号转导子和转录激活子（STAT）-3的磷酸化、细胞内Ca²⁺浓度以及蛋白激酶C（PKC）的磷酸化。JAK2特异性小干扰RNA（siRNA）、一种STAT3抑制剂、星形孢菌素和双吲哚马来酰亚胺I（PKC抑制剂）可阻断IL-6诱导的2-DG摄取增加和GLUT-2蛋白表达。此外，IL-6增加了表皮生长因子受体（EGFR）/src/黏着斑激酶（FAK）、磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（Akt）的磷酸化以及2-DG摄取和GLUT-2蛋白表达，而AG 1478（EGF受体抑制剂）、PP2（src家族酪氨酸激酶抑制剂）、PI3K特异性siRNA和一种Akt抑制剂可阻断这些作用。此外，IL-6增加了p44/42丝裂原活化蛋白激酶（MAPKs）的磷酸化，p44和p42 MAPK特异性siRNA混合物可阻断IL-6诱导的2-DG摄取增加和GLUT-2蛋白表达。总之，在原代培养鸡肝细胞中，IL-6通过Ca²⁺/PKC和EGF受体激活p44/42 MAPKs来刺激2-DG摄取。
