Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis.
Glucorticoids reduce eosinophilia through a direct effect on eosinophils or indirectly on cells producing cytokines and chemokines. Conflicting data have been previously reported concerning glucocorticoid effects on eosinopoiesis. To elucidate this point, dexamethasone was added during eosinophil differentiation of CD34+ cells. Dexamethasone enhanced proliferation and differentiation through an early effect on immature cells. Dexamethasone inhibited apoptosis during early differentiation, whereas death of mature cells was increased. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor involved in the proliferation, differentiation and survival of haematopoietic cells, which interacts with glucocorticoid receptor. Activation of STAT5 by interleukin-5 was investigated during eosinophil differentiation. Long isoforms of STAT5 were activated during the entire period in the culture as well as in blood eosinophils, while short isoforms were only activated during early differentiation. Short isoforms were less activated in the presence of dexamethasone. This suggests that dexamethasone could act on proliferation, differentiation and apoptosis during eosinophil differentiation through an association of STAT5 with the glucocorticoid receptor.
Debierre-Grockiego
Françoise
F
Institute for Virology, Medical Centre for Hygiene, Philipps University, Marburg, Germany. debierre@mailer.uni-marburg.de
Fuentes
Vincent
V
Prin
Lionel
L
Gouilleux
Fabrice
F
Gouilleux-Gruart
Valérie
V
D018952:Antigens, CD34; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005312:Fetal Blood; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D019891:Leukopoiesis; D008894:Milk Proteins; D020033:Protein Isoforms / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D013268:Stimulation, Chemical; D015534:Trans-Activators / Q000378:metabolism*
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D015848:Interleukin-5; D008894:Milk Proteins; D020033:Protein Isoforms; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D003907:Dexamethasone