Premium
Interleukin‐6 promotes 2‐deoxyglucose uptake through p44/42 MAPKs activation via Ca 2+ /PKC and EGF receptor in primary cultured chicken hepatocytes
Author(s) -
Suh Han Na,
Lee Yu Jin,
Han Ho Jae
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21641
Subject(s) - protein kinase c , bisindolylmaleimide , phosphorylation , cycloheximide , microbiology and biotechnology , ly294002 , protein kinase b , biology , signal transduction , stat3 , tyrosine phosphorylation , pi3k/akt/mtor pathway , staurosporine , protein biosynthesis
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‐ (≥4 h) and a dose ‐(≥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‐6Rα and glycoprotein (gp) 130 (IL‐6Rβ) 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. J. Cell. Physiol. 218: 643–652, 2009. © 2008 Wiley‐Liss, Inc.