In Vitro Effects of Budesonide on Eosinophil-Basophil Lineage Commitment
Michael M Cyr†1, Adrian J Baatjes†1, Sandra C Dorman§1, Lynn Crawford1, Roma Sehmi1, Ronan Foley1, Rafeul Alam2, Paul O’ Byrne1, Judah A Denburg*, 1
1 Division of Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada
2 Division of Allergy & Immunology, National Jewish Medical & Research Center, Denver, CO, USA
IL-5 is the primary cytokine that stimulates the production and survival of eosinophils and basophils from progenitor cells. The inhaled glucocorticoid, budesonide, has been shown to exert a therapeutic effect via suppression of eosinophil/basophil progenitors in vivo. Since various steroids have exhibited the ability to enhance eosinophil/basophil progenitor differentiation, we examined the effects of budesonide in vitro. Bone marrow and cord blood samples were obtained and cultured in the presence of IL-5 alone or IL-5 plus budesonide. Eosinophil/basophil colony-forming units were enumerated from cultured nonadherent mononuclear cells and from purified CD34+ cells. CD34+ cells with and without budesonide were also examined for up-regulation of ERK1/2, MAPK and GATA-1 using real time-PCR. Results: i) up-regulation of eosinophil/basophil colony-forming units is due to the direct effects of budesonide on IL-5-stimulated progenitors; ii) GATA-1 is likely involved in the early amplification of eosinophil/basophil progenitor commitment leading to increased differentiation. A potential transcriptional pathway has been identified which may mediate the effects of budesonide on eosinophil/basophil lineage commitment.
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* Address correspondence to this author at the Division of Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada; E-mail: email@example.com;firstname.lastname@example.org†M.M. Cyr and A.J. Baatjes are co-first authors on this paper. §Present Address: School of Human Kinetics, Laurentian University, Sudbury, ON, Canada