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


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© Cyr et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Division of Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada; E-mail: denburg@mcmaster.ca;larocque@mcmaster.ca
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


Abstract

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.

Keywords: Budesonide, eosinophil/basophil progenitors, corticosteroids, GATA-1, IL-5..