Differential control of eosinophil survival by glucocorticoids

John W Bloom, J. Chacko, I. C. Lohman, M. Halonen, Fernando Martinez, Roger Miesfeld

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Glucocorticoids are effective drugs for eosinophil-related disorders, such as asthma and allergy. Previous studies have demonstrated that glucocorticoids increase eosinophil apoptosis and block the survival effect of submaximal concentrations of interleukin-5 (IL-5). We investigated the effect of glucocorticoids on eosinophil survival in the presence of a higher concentration of IL-5 (1 ng/ml), comparable to IL-5 levels in bronchoalveolar lavage and sputum specimens from patients with asthma. In contrast to incubation in the presence of submaximal concentrations of IL-5, the addition of dexamethasone (DEX) to media containing I ng/ml IL-5 led to a significant increase in eosinophil cell viability from 58 ± 6.9% to 87 ± 2.4% (p < 0.005) after 72 hours in culture. We found that RU486 blocked the DEX effect on cell viability confirming that glucocorticoid receptor functions are required. We Investigated the possibility that the glucocorticoid enhancement of eosinophil survival may be due to an effect on IL-5 receptor expression. Our results show that the IL-5 associated decrease in IL-5 receptor α-subunit expression was blocked significantly after 24 hrs in culture with media containing IL-5 plus DEX compared to IL-5 alone. It is tempting to speculate that the observed glucocorticoid enhancement of eosinophil survival in the presence of elevated concentrations of IL-5 could be a mechanism that contributes to glucocorticoid resistance in asthma.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalApoptosis
Volume9
Issue number1
DOIs
StatePublished - Jan 2004

Fingerprint

Interleukin-5
Eosinophils
Glucocorticoids
Interleukin-5 Receptors
Dexamethasone
Asthma
Cell Survival
Cells
Allergies
Glucocorticoid Receptors
Bronchoalveolar Lavage
Sputum
Interleukin-1
Culture Media
Hypersensitivity
Apoptosis
Survival

Keywords

  • Eosinophil
  • Glucocorticoids
  • Interleukin-5

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Differential control of eosinophil survival by glucocorticoids. / Bloom, John W; Chacko, J.; Lohman, I. C.; Halonen, M.; Martinez, Fernando; Miesfeld, Roger.

In: Apoptosis, Vol. 9, No. 1, 01.2004, p. 97-104.

Research output: Contribution to journalArticle

Bloom, John W ; Chacko, J. ; Lohman, I. C. ; Halonen, M. ; Martinez, Fernando ; Miesfeld, Roger. / Differential control of eosinophil survival by glucocorticoids. In: Apoptosis. 2004 ; Vol. 9, No. 1. pp. 97-104.
@article{bb9b3350f6c54887b277b40c1666ab2f,
title = "Differential control of eosinophil survival by glucocorticoids",
abstract = "Glucocorticoids are effective drugs for eosinophil-related disorders, such as asthma and allergy. Previous studies have demonstrated that glucocorticoids increase eosinophil apoptosis and block the survival effect of submaximal concentrations of interleukin-5 (IL-5). We investigated the effect of glucocorticoids on eosinophil survival in the presence of a higher concentration of IL-5 (1 ng/ml), comparable to IL-5 levels in bronchoalveolar lavage and sputum specimens from patients with asthma. In contrast to incubation in the presence of submaximal concentrations of IL-5, the addition of dexamethasone (DEX) to media containing I ng/ml IL-5 led to a significant increase in eosinophil cell viability from 58 ± 6.9{\%} to 87 ± 2.4{\%} (p < 0.005) after 72 hours in culture. We found that RU486 blocked the DEX effect on cell viability confirming that glucocorticoid receptor functions are required. We Investigated the possibility that the glucocorticoid enhancement of eosinophil survival may be due to an effect on IL-5 receptor expression. Our results show that the IL-5 associated decrease in IL-5 receptor α-subunit expression was blocked significantly after 24 hrs in culture with media containing IL-5 plus DEX compared to IL-5 alone. It is tempting to speculate that the observed glucocorticoid enhancement of eosinophil survival in the presence of elevated concentrations of IL-5 could be a mechanism that contributes to glucocorticoid resistance in asthma.",
keywords = "Eosinophil, Glucocorticoids, Interleukin-5",
author = "Bloom, {John W} and J. Chacko and Lohman, {I. C.} and M. Halonen and Fernando Martinez and Roger Miesfeld",
year = "2004",
month = "1",
doi = "10.1023/B:APPT.0000012126.06126.c4",
language = "English (US)",
volume = "9",
pages = "97--104",
journal = "Apoptosis : an international journal on programmed cell death",
issn = "1360-8185",
publisher = "Springer Netherlands",
number = "1",

}

TY - JOUR

T1 - Differential control of eosinophil survival by glucocorticoids

AU - Bloom, John W

AU - Chacko, J.

AU - Lohman, I. C.

AU - Halonen, M.

AU - Martinez, Fernando

AU - Miesfeld, Roger

PY - 2004/1

Y1 - 2004/1

N2 - Glucocorticoids are effective drugs for eosinophil-related disorders, such as asthma and allergy. Previous studies have demonstrated that glucocorticoids increase eosinophil apoptosis and block the survival effect of submaximal concentrations of interleukin-5 (IL-5). We investigated the effect of glucocorticoids on eosinophil survival in the presence of a higher concentration of IL-5 (1 ng/ml), comparable to IL-5 levels in bronchoalveolar lavage and sputum specimens from patients with asthma. In contrast to incubation in the presence of submaximal concentrations of IL-5, the addition of dexamethasone (DEX) to media containing I ng/ml IL-5 led to a significant increase in eosinophil cell viability from 58 ± 6.9% to 87 ± 2.4% (p < 0.005) after 72 hours in culture. We found that RU486 blocked the DEX effect on cell viability confirming that glucocorticoid receptor functions are required. We Investigated the possibility that the glucocorticoid enhancement of eosinophil survival may be due to an effect on IL-5 receptor expression. Our results show that the IL-5 associated decrease in IL-5 receptor α-subunit expression was blocked significantly after 24 hrs in culture with media containing IL-5 plus DEX compared to IL-5 alone. It is tempting to speculate that the observed glucocorticoid enhancement of eosinophil survival in the presence of elevated concentrations of IL-5 could be a mechanism that contributes to glucocorticoid resistance in asthma.

AB - Glucocorticoids are effective drugs for eosinophil-related disorders, such as asthma and allergy. Previous studies have demonstrated that glucocorticoids increase eosinophil apoptosis and block the survival effect of submaximal concentrations of interleukin-5 (IL-5). We investigated the effect of glucocorticoids on eosinophil survival in the presence of a higher concentration of IL-5 (1 ng/ml), comparable to IL-5 levels in bronchoalveolar lavage and sputum specimens from patients with asthma. In contrast to incubation in the presence of submaximal concentrations of IL-5, the addition of dexamethasone (DEX) to media containing I ng/ml IL-5 led to a significant increase in eosinophil cell viability from 58 ± 6.9% to 87 ± 2.4% (p < 0.005) after 72 hours in culture. We found that RU486 blocked the DEX effect on cell viability confirming that glucocorticoid receptor functions are required. We Investigated the possibility that the glucocorticoid enhancement of eosinophil survival may be due to an effect on IL-5 receptor expression. Our results show that the IL-5 associated decrease in IL-5 receptor α-subunit expression was blocked significantly after 24 hrs in culture with media containing IL-5 plus DEX compared to IL-5 alone. It is tempting to speculate that the observed glucocorticoid enhancement of eosinophil survival in the presence of elevated concentrations of IL-5 could be a mechanism that contributes to glucocorticoid resistance in asthma.

KW - Eosinophil

KW - Glucocorticoids

KW - Interleukin-5

UR - http://www.scopus.com/inward/record.url?scp=1442350549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1442350549&partnerID=8YFLogxK

U2 - 10.1023/B:APPT.0000012126.06126.c4

DO - 10.1023/B:APPT.0000012126.06126.c4

M3 - Article

C2 - 14739603

AN - SCOPUS:1442350549

VL - 9

SP - 97

EP - 104

JO - Apoptosis : an international journal on programmed cell death

JF - Apoptosis : an international journal on programmed cell death

SN - 1360-8185

IS - 1

ER -