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Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids
Joint Authors
Alvarez-Mon, Melchor
Escoll, Pedro
Ranz, Ismael
Muñoz-Antón, Norman
van-den-Rym, Ana
Martínez-Alonso, Carlos
Sanz, Eva
de-la-Hera, Antonio
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-04-22
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Clinical treatment with glucocorticoids (GC) can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR), a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR-) driven anti-inflammatory genes.
However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently.
As sustained IL-1β exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1β and afterwards challenged with GC.
After a GC challenge, sustained IL-1β exposure reduced the cytoplasmic GR level, GRSer203 and GRSer211 phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes.
Compared to GC alone, in a broad range of GC doses plus sustained IL-1β, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down.
In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold.
These effects were cytokine-selective, IL-1β dose- and IL-1R1-dependent.
The integrated gain and loss of gene functions in the “split GCR” model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.
American Psychological Association (APA)
Escoll, Pedro& Ranz, Ismael& Muñoz-Antón, Norman& van-den-Rym, Ana& Alvarez-Mon, Melchor& Martínez-Alonso, Carlos…[et al.]. 2015. Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids. Mediators of Inflammation،Vol. 2015, no. 2015, pp.1-16.
https://search.emarefa.net/detail/BIM-1072259
Modern Language Association (MLA)
Escoll, Pedro…[et al.]. Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids. Mediators of Inflammation No. 2015 (2015), pp.1-16.
https://search.emarefa.net/detail/BIM-1072259
American Medical Association (AMA)
Escoll, Pedro& Ranz, Ismael& Muñoz-Antón, Norman& van-den-Rym, Ana& Alvarez-Mon, Melchor& Martínez-Alonso, Carlos…[et al.]. Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids. Mediators of Inflammation. 2015. Vol. 2015, no. 2015, pp.1-16.
https://search.emarefa.net/detail/BIM-1072259
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1072259