Glucocorticoids inhibit IL-4 and mitogen-induced IL-4Rα chain expression by different posttranscriptional mechanisms☆,☆☆,★,★★,♢
Section snippets
Reagents
Human recombinant IL-4 (rIL-4) was purchased from Genzyme Corp (Cambridge, Mass). PMA and dexamethasone were from Sigma Chemical Co (St Louis, Mo). PMA was dissolved in dimethyl sulfoxide, and dexamethasone was water soluble. The glucocorticoid antagonist RU486 was provided by Roussel Uclaf (Romainville, France) and was dissolved in ethanol. PMA and RU486 were diluted in culture medium, and the final concentration of dimethyl sulfoxide and ethanol in cultures was less than 0.01%. Actinomycin D
Decreased IL-4Rα protein expression by dexamethasone
The effect of dexamethasone on the IL-4Rα expression induced by means of protein kinase C (PKC) by PMA was analyzed by flow cytometry with the IL-4Rα–specific mAb M57 in both freshly isolated PBMCs and in highly purified T cells (Table I, Fig 1).
Empty Cell IL-4Rα MFI Empty Cell 24 h 48 h 72 h PBMCs Medium 7.00 ± 2.16 16.00 ± 2.16 14.33 ± 6.18 PMA 24.00 ± 6.24 28.00 ± 4.35 36.33 ± 15.04 PMA + DEX 6.00 ± 1.73* 15.66 ± 0.57* 9.33 ± 3.51 T cells Medium 5.66
DISCUSSION
Regulation of immunoresponses by glucocorticoids is widely due to their capacity to enhance or repress the production of cytokines and their receptors. In this study a dexamethasone-mediated downregulation of PMA- or IL-4-induced IL-4Rα expression is described, and evidence is also shown that the glucocorticoid modulates IL-4Rα levels by different regulatory mechanisms, depending on the nature of the activation signal.
Pharmacologic doses of dexamethasone clearly exerted a downmodulatory effect
Acknowledgements
The authors thank Dr S. Gillis and Dr P. Beckmann for providing the IL-4R cDNA probe and the M57 mAb, Roussel Uclaf for the supply of RU 486, Dr Achsah D. Keegan for the critical reading of the manuscript, and David Wallace for the English correction.
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Cited by (0)
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From a the Department of Immunology, Hospital Central de Asturias, Centro Universitario, Oviedo; and b Functional Biology, Universidad de Oviedo, Oviedo.
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José Zamorano is currently affiliated with the Immunology Department, American Red Cross, Rockville, Md.
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Supported by Grants FIS 92/102 and 97/955 from the Fondo de Investigaciones Sanitarias de la Seguridad Social.
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Reprint requests: Carmen Gutiérrez, MD, Servicio de Inmunología, Hospital Central de Asturias, Julián Clavería s/n, 33006 Oviedo, Spain.
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0091-6749/98 $5.00 + 0 1/1/93728