TY - JOUR
T1 - Role of interleukin-6 in the control of DNA synthesis of hepatocytes
T2 - Involvement of PKC, p44/42 MAPKs, and PPARδ
AU - Suh, Han Na
AU - Lee, Sang Hun
AU - Lee, Min Young
AU - Lee, Yu Jin
AU - Lee, Jang Hern
AU - Han, Ho Jae
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Hepatocytes proliferation
KW - Interleukin-6
KW - p44/42 MAPKs
KW - PKC
KW - PPARδ
UR - http://www.scopus.com/inward/record.url?scp=57649196331&partnerID=8YFLogxK
U2 - 10.1159/000185551
DO - 10.1159/000185551
M3 - Article
C2 - 19088449
AN - SCOPUS:57649196331
SN - 1015-8987
VL - 22
SP - 673
EP - 684
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
IS - 5-6
ER -