Why is erythropoietin present in human milk? Studies of erythropoietin receptors on enterocytes of human and rat neonates.
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.
Juul
S E
SE
Department of Pediatrics, University of Florida, College of Medicine, Gainesville 32610-0296, USA.
Joyce
A E
AE
Zhao
Y
Y
Ledbetter
D J
DJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004921:Erythropoietin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D008895:Milk, Human / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017467:Receptors, Erythropoietin / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin