[The effects and mechanisms of erythropoietin on hepcidin of human monocytes].
OBJECTIVE
To investigate the in vitro effect of erythropoietin (EPO) on hepcidin of monocytes and its molecular mechanisms.


METHODS
Hepcidin and signaling molecules including C/EBPalpha, Smad1/5/8, p-Smad1/5/8 and p-STAT3 were detected by real time PCR and Western blot. THP-1 monocytes were stimulated by interleukin-6 (IL-6) or lipopolysaccharide (LPS). EPO receptor (EPOR) antibody was added to observe its antagonistic effect on EPO and impact on the signaling proteins.


RESULTS
EPO suppressed mRNA expression of THP-1 hepcidin of monocytes induced by 20 ng/ml IL-6 or 1 microg/ml LPS in both dose and time dependent manner. The most decrease of hepcidin expression was observed at 2 IU/ml EPO for 6 hours. EPO also down-regulated hepcidin protein induced by 20 ng/ml IL-6. At 2 IU/ml EPO for 6 hours hepcidin protein was down-regulated, as was C/EBPalpha, p-Smad1/5/8 and p-STAT3. Antibody to EPOR antagonized the down-regulation of EPO on hepcidin and signaling proteins.


CONCLUSIONS
Monocytes hepcidin can be reduced by EPO when stimulated by IL-6 or LPS. The mechanism of which may be at least in part, via suppression of C/EBPalpha, p-Smad1/5/8 and p-STAT3 signaling.
Department of Hematology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China.
Xiao
X
Han
Dao-Bin
DB
Zhou
Cai-Min
CM
Xu
Yang
Y
Yang
Ming-Hui
MH
Duan
Xuan
X
Wang
Jie-Ping
JP
Zhang
Yong-Qiang
YQ
Zhao
Ti
T
Shen
Yong-Ji
YJ
Wu
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002478:Cells, Cultured; D004921:Erythropoietin / Q000494:pharmacology*; D064451:Hepcidins; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D004921:Erythropoietin