Why is erythropoietin present in human milk? Studies of erythropoietin receptors on enterocytes of human and rat neonates

Pediatr Res. 1999 Sep;46(3):263-8. doi: 10.1203/00006450-199909000-00003.


Erythropoietin receptors (Epo-R) are expressed on cells in the small bowel of human fetuses, but their function has not been defined. We hypothesized that intestinal Epo-R are present postnatally, and that recombinant erythropoietin (rEpo) would increase enterocyte migration and decrease cytokine-induced apoptosis. We used reverse transcriptase-polymerase chain reaction and immunohistochemistry to evaluate the presence of Epo-R mRNA and protein in rat intestinal epithelial cells (IEC-6), and in postnatal human and rat bowel. The effect of rEpo on rates of cell migration and proliferation were established in IEC-6 cells by using cell counting and incorporation of bromodeoxyuridine. To determine whether rEpo affects response to injury, cells were pretreated with rEpo, then were damaged with 25 or 50 ng/mL tumor necrosis factor-alpha plus 2.5 microg/mL cycloheximide. Cell death was determined by colorimetric bioassay. We found that Epo-R mRNA and protein were expressed by IEC-6 cells and by enterocytes of postnatal rat and human small bowel. Cells that had been exposed to 0.05 or 5.00 U/mL rEpo migrated faster than did the controls (p < 0.05), but no difference was noted in cell proliferation. Treatment of IEC-6 cells with rEpo before or at the time of injury resulted in a lower percentage of cell death, and this effect was neutralized by anti-Epo antibody. We conclude that Epo-R is expressed in enterocytes postnatally in rats and humans. Recombinant Epo increases the rate of migration of IEC-6 cells and decreases cytokine-induced apoptosis. These studies suggest that Epo within human milk has actions on neonate's intestinal function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cytokines / pharmacology
  • Erythropoietin / metabolism*
  • Erythropoietin / pharmacology
  • Humans
  • Infant, Newborn
  • Intestinal Mucosa / embryology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Milk, Human / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Receptors, Erythropoietin / analysis
  • Receptors, Erythropoietin / metabolism*
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology


  • Cytokines
  • RNA, Messenger
  • Receptors, Erythropoietin
  • Recombinant Proteins
  • Erythropoietin