Document Detail

Oncostatin M and leukemia inhibitory factor increase hepcidin expression in hepatoma cell lines.
MedLine Citation:
PMID:  19915946     Owner:  NLM     Status:  MEDLINE    
Overproduction of hepcidin by interleukin-6 (IL-6) is considered to be the main factor responsible for the development of anemia in inflammatory conditions. Since oncostatin M (OSM), a member of the IL-6 family, plays an important role in immune and inflammatory responses, we assessed the effect of OSM on hepcidin expression, as well as that of leukemia inhibitory factor (LIF), another member of the IL-6 family. We found that hepcidin expression was markedly induced by OSM and LIF in a time- and dose-dependent manner in hepatoma cell lines, and this expression was induced independent of IL-6/IL-6 receptor signaling. Luciferase assay revealed that OSM and LIF stimulated a -1.3-kb hepcidin promoter. This effect was markedly reduced when the signal transducer and activator of transcription (STAT) site of the promoter was mutated, and was almost completely abolished in the presence of AG-490, a Janus kinase (JAK) inhibitor. Hence, the JAK/STAT pathway plays a major role in OSM- and LIF-induced activation of the hepcidin promoter. In conclusion, we demonstrated that OSM and LIF can induce hepcidin expression mainly through the JAK/STAT pathways. Further studies are warranted to evaluate the clinical significance of OSM and LIF in the development of anemia in various inflammatory diseases.
Junya Kanda; Tatsuki Uchiyama; Naohisa Tomosugi; Masato Higuchi; Takashi Uchiyama; Hiroshi Kawabata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-14
Journal Detail:
Title:  International journal of hematology     Volume:  90     ISSN:  1865-3774     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-03-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  545-52     Citation Subset:  IM    
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
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MeSH Terms
Antimicrobial Cationic Peptides / biosynthesis*
Carcinoma, Hepatocellular / pathology*
Cell Line, Tumor
Dose-Response Relationship, Drug
Leukemia Inhibitory Factor / pharmacology*
Oncostatin M / pharmacology*
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/LIF protein, human; 0/Leukemia Inhibitory Factor; 0/hepcidin; 106956-32-5/Oncostatin M

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