The effects and mechanisms of erythropoietin on hepcidin of human monocytes / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the in vitro effect of erythropoietin (EPO) on hepcidin of monocytes and its molecular mechanisms.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>