Role of interleukin-6 in the control of DNA synthesis of hepatocytes: Involvement of PKC, p44/42 MAPKs, and PPARδ

Han Na Suh, Sang Hun Lee, Min Young Lee, Yu Jin Lee, Jang Hern Lee, Ho Jae Han

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 (≥ 6 hr)- and a dose (≥ 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-6Rα and glycoprotein (gp) 130 (IL-6Rβ) protein expression, Janus Kinase (JAK) 2, signal transducer and activator of transcription (STAT) 3, PKC, p44/42 MAPKs phosphorylation, and PPARδ 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 PPARδ-specific small interfering RNAs (siRNAs). In conclusion, IL-6 stimulates the proliferation of primary cultured chicken hepatocytes through PKC, p44/42 MAPKs, and PPARδ pathways.

Original languageEnglish
Pages (from-to)673-684
Number of pages12
JournalCellular Physiology and Biochemistry
Volume22
Issue number5-6
DOIs
StatePublished - 2008

Keywords

  • Hepatocytes proliferation
  • Interleukin-6
  • p44/42 MAPKs
  • PKC
  • PPARδ

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