Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis

Françoise Debierre-Grockiego (1) , Vincent Fuentes (2) , Lionel Prin (3) , Fabrice Gouilleux (2) , Valérie Gouilleux-Gruart (2)

1 Philipps Universität Marburg = Philipps University of Marburg
2 UPJV - Université de Picardie Jules Verne
3 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]

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.

Domaines: Sciences du Vivant [q-bio]

Françoise Debierre-Grockiego, Vincent Fuentes, Lionel Prin, Fabrice Gouilleux, Valérie Gouilleux-Gruart. Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis. British Journal of Haematology, 2003, 123 (5), pp.933-941. ⟨10.1046/j.1365-2141.2003.04700.x⟩. ⟨hal-02427350⟩