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In vitro effects of budesonide on eosinophil-basophil lineage commitment.

Cyr MM, Baatjes AJ, Dorman SC, Crawford L, Sehmi R, Foley R, Alam R, Byrne PO, Denburg JA - Open Respir Med J (2008)

Bottom Line: 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.A potential transcriptional pathway has been identified which may mediate the effects of budesonide on eosinophil/basophil lineage commitment.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada.

ABSTRACT

Unlabelled: 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.

No MeSH data available.


Related in: MedlinePlus

Effect of BUD on IL-5-stimulated GATA-1 expression. The graph summarizes the kinetics of GATA-1 expression in IL-5-stimulated CB hemopoietic progenitors. The effect of BUD on GATA-1 is shown in hatched bars.
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Figure 4: Effect of BUD on IL-5-stimulated GATA-1 expression. The graph summarizes the kinetics of GATA-1 expression in IL-5-stimulated CB hemopoietic progenitors. The effect of BUD on GATA-1 is shown in hatched bars.

Mentions: IL-5 alone induces GATA-1 up-regulation in CB NAMNC, which peaks at 48 hours post-stimulation, with a 12.3 fold (±4.3) increase from baseline. The addition of BUD at a concentration of 10-8M resulted in an early enhancement of GATA-1 expression at 4 hours, with a fold increase of 11.5 (±6.8), followed by an inhibitory effect at 8 hours (3.2±1.3), returning to baseline levels at 24 hours (2.4±1.0). All results are in comparison to un-stimulated CB cells (Fig. 4).


In vitro effects of budesonide on eosinophil-basophil lineage commitment.

Cyr MM, Baatjes AJ, Dorman SC, Crawford L, Sehmi R, Foley R, Alam R, Byrne PO, Denburg JA - Open Respir Med J (2008)

Effect of BUD on IL-5-stimulated GATA-1 expression. The graph summarizes the kinetics of GATA-1 expression in IL-5-stimulated CB hemopoietic progenitors. The effect of BUD on GATA-1 is shown in hatched bars.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2606647&req=5

Figure 4: Effect of BUD on IL-5-stimulated GATA-1 expression. The graph summarizes the kinetics of GATA-1 expression in IL-5-stimulated CB hemopoietic progenitors. The effect of BUD on GATA-1 is shown in hatched bars.
Mentions: IL-5 alone induces GATA-1 up-regulation in CB NAMNC, which peaks at 48 hours post-stimulation, with a 12.3 fold (±4.3) increase from baseline. The addition of BUD at a concentration of 10-8M resulted in an early enhancement of GATA-1 expression at 4 hours, with a fold increase of 11.5 (±6.8), followed by an inhibitory effect at 8 hours (3.2±1.3), returning to baseline levels at 24 hours (2.4±1.0). All results are in comparison to un-stimulated CB cells (Fig. 4).

Bottom Line: 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.A potential transcriptional pathway has been identified which may mediate the effects of budesonide on eosinophil/basophil lineage commitment.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada.

ABSTRACT

Unlabelled: 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.

No MeSH data available.


Related in: MedlinePlus