Leukemia inhibitory factor enhances bFGF-induced IL-6 synthesis in osteoblasts: involvement of JAK2/STAT3.
We previously showed that basic fibroblast growth factor (bFGF) stimulates release of vascular endothelial growth factor (VEGF) and synthesis of interleukin-6 (IL-6) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of leukemia inhibitory factor (LIF) on the release of VEGF and IL-6 in these cells. LIF did not affect the bFGF-stimulated VEGF release. On the contrary, LIF, which alone had little effect on IL-6 release, significantly enhanced the bFGF-stimulated IL-6 release. The amplifying effect of LIF on the IL-6 release was dose dependent in the range between 0.01 and 10 ng/ml. AG490, an inhibitor of JAK2, suppressed the amplifying effect of LIF. LIF induced the phosphorylation of STAT3. AG490 inhibited the LIF-induced STAT3 phosphorylation. Taken together, our results strongly suggest that LIF enhances bFGF-stimulated IL-6 synthesis via JAK2/STAT3 pathway in osteoblasts.
Kozawa
Osamu
O
Department of Pharmacology, Gifu University School of Medicine, 500-8705, Gifu, Japan. okozawa@cc.gifu-u.ac.jp
Otsuka
Takanobu
T
Uematsu
Toshihiko
T
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D053614:Janus Kinase 2; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D020032:Tyrphostins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D016222:Fibroblast Growth Factor 2; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2