Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/12763
Title: Dexamethasone prevents interleukin-1beta-induced nuclear factor-kappaB activation by upregulating IkappaB-alpha synthesis, in lymphoblastic cells
Authors: Castro-Caldas, M. 
Mendes, A. F. 
Carvalho, A. P. 
Duarte, C. B. 
Lopes, M. C. 
Keywords: Nuclear factor-kB; Dexamethasone; IkB-a; Interleukin-1b; Lymphoblastic cells
Issue Date: Feb-2003
Publisher: Taylor & Francis Ltd
Citation: Mediators of Inflammation. 12:1 (2003) 37-46
Abstract: AIMS: Glucocorticoids (GCs) exert some of their anti-inflammatory actions by preventing the activation of the transcription factor nuclear factor (NF)-kappaB. The GC-dependent inhibition of NF-kappaB may occur at different levels, but the mechanisms involved are still incompletely understood. In this work, we investigated whether the synthetic GC, dexamethasone (Dex), modulates the activity of NF-kappaB in the lymphoblastic CCRF-CEM cell line. We also evaluated the ability of Dex to prevent the activation of NF-kappaB in response to the potent proinflammatory cytokine, interleukin (IL)-1beta. RESULTS: Exposure of the cells to Dex (1 microM) induced the rapid degradation of IkappaB-alpha, leading to the transient translocation of the NF-kappaB family members p65 and p50 from the cytoplasm to the nucleus, as evaluated by western blot. Electrophoretic mobility shift assays revealed that, in the nucleus, these NF-kappaB proteins formed protein-DNA complexes, indicating a transient activation of NF-kappaB. Additionally, Dex also induced de novo synthesis of IkappaB-alpha, following its degradation. Finally, when the cells were exposed to Dex (1 microM) prior to stimulation with IL-1beta (20 ng/ml), Dex was efficient in preventing IL-1beta-induced NF-kappaB activation. The GC antagonist, RU 486 (10 microM), did not prevent any of the effects of Dex reported here. CONCLUSION: Our results indicate that, in CCRF-CEM cells, Dex prevents NF-kappaB activation, induced by IL-1beta, by a mechanism that involves the upregulation of IkappaB-alpha synthesis, and that depends on the early and transient activation of NF-kappaB
URI: http://hdl.handle.net/10316/12763
ISSN: 0962-9351
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
Dexamethasone prevents interleukin-1beta-induced.pdf487.24 kBAdobe PDFView/Open
Show full item record

Page view(s)

125
checked on Jun 3, 2020

Download(s) 50

484
checked on Jun 3, 2020

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.