title: Role of interleukin-6 in the control of DNA synthesis of hepatocytes: involvement of PKC, p44/42 MAPKs, and PPARdelta.
abstract: Interleukin-6 (IL-6) is a pleiotropic cytokine with a pivotal role in normal hepatic growth and liver regeneration. Therefore, in the present study, we examined the effect of IL-6 on cell proliferation and the related signaling pathways in primary cultured chicken hepatocytes. IL-6 increased the level of [(3)H]thymidine incorporation in a time (>or= 6 hr)- and a dose (>or= 0.1 ng/ml)-dependent manner. Indeed, IL-6 increased the number of BrdU-positive cells and the total number of cells. IL-6 (10 ng/ml) increased the level of IL-6Ralpha and glycoprotein (gp) 130 (IL-6Rbeta) protein expression, Janus Kinase (JAK) 2, signal transducer and activator of transcription (STAT) 3, PKC, p44/42 MAPKs phosphorylation, and PPARdelta protein expression. Inhibition of each pathways blocked IL-6-induced [(3)H]thymidine incorporation increase. IL-6 increased c-fos, c-jun, and c-myc proto-oncogene mRNA levels and the percentage of cells in the S phase according to fluorescence-activated cell sorter (FACS) analysis. IL-6-induced G1/S phase progression was inhibited by AG 490 (2x10(-5) M, JAK2 inhibitor), a STAT3 inhibitor peptide (10(-5) M), bisindolylmaleimide I (10(-6) M, PKC inhibitor), PD 98059 (10(-5) M, p44/42 MAPKs blocker), or PPARdelta-specific small interfering RNAs (siRNAs). In conclusion, IL-6 stimulates the proliferation of primary cultured chicken hepatocytes through PKC, p44/42 MAPKs, and PPARdelta pathways.
authors.affiliation: Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors.forename: Han Na
authors.initials: HN
authors.lastname: Suh
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jang Hern
authors.initials: JH
authors.lastname: Lee
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D004247:DNA / Q000096:biosynthesis*; 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; D047494:PPAR delta / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D015850:Interleukin-6; C000715470:MAS1 protein, human; D047494:PPAR delta; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019947:Receptors, Interleukin-6; D050791:STAT Transcription Factors; D004247:DNA; D053612:Janus Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3