title: Interleukin-6 promotes 2-deoxyglucose uptake through p44/42 MAPKs activation via Ca2+/PKC and EGF receptor in primary cultured chicken hepatocytes.
abstract: 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.
authors.affiliation: Department of Veterinary Physiology, Biotherapy Human Resources Center (BK21), College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea.
authors.forename: Han Na
authors.initials: HN
authors.lastname: Suh
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D003847:Deoxyglucose / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D015850:Interleukin-6 / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050791:STAT Transcription Factors; D003847:Deoxyglucose; D066246:ErbB Receptors; D053612:Janus Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium