Differential control of eosinophil survival by glucocorticoids.
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 1 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 alpha-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.
Bloom
J W
JW
Arizona Respiratory Center and the Department of Pharmacology at the University of Arizona, Tucson, AZ 85724, USA. jbloom@resp-sci.arizona.edu
Chacko
J
J
Lohman
I C
IC
Halonen
M
M
Martinez
F D
FD
Miesfeld
R L
RL
D000328:Adult; D017209:Apoptosis; D001249:Asthma / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D003470:Culture Media / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D053666:Interleukin-5 Receptor alpha Subunit; D015735:Mifepristone / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000378:metabolism; D013997:Time Factors
D003470:Culture Media; D005938:Glucocorticoids; D006727:Hormone Antagonists; C485918:IL5RA protein, human; D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit; D018123:Receptors, Interleukin; D015735:Mifepristone; D003907:Dexamethasone; D020169:Caspases