title: Erythropoietin exerts anti-apoptotic effects on rat microglial cells in vitro.
abstract: Erythropoietin (EPO), a renal cytokine regulating haematopoiesis, is also produced by different cell types within the central nervous system, where it acts via the activation of specific receptors. Current evidence shows that EPO exerts neurotrophic and neuroprotective activities in different in vivo and in vitro models of brain damage. In the present study we investigated the effects of EPO on primary cultures of rat cortical microglia and astrocytes. We found that: (i) EPO exerted a marked stimulatory effect on microglial cell viability, assessed through the MTS assay, whereas astrocytes were almost unaffected; (ii) the cytokine increased microglial cell population size in a concentration-dependent manner; however, as microglia cultures undergo spontaneous apoptosis after separation from astrocytes, the apparent effect on cell proliferation could be attributed to EPO antagonism of normal apoptosis; (iii) subsequent flow cytometry analysis on microglial cells demonstrated both the trophic role of factor(s) released by astrocytes in mixed cultures, and the putative anti-apoptotic action of EPO; (iv) the latter was further confirmed through the assessment of gene expression of anti- and pro-apoptotic factors, which showed that EPO is able to shift the Bcl : Bax ratio towards a net anti-apoptotic effect; (v) EPO did not affect the pro-inflammatory function of microglial cells.
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Vairano
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dello Russo
authors.forename: Giacomo
authors.initials: G
authors.lastname: Pozzoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Battaglia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tringali
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Aloe-Spiriti
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin