Dexamethasone-induced and estradiol-induced CREB activation and annexin 1 expression in CCRF-CEM lymphoblastic cells: evidence for the involvement of cAMP and p38 MAPKReport as inadecuate




Dexamethasone-induced and estradiol-induced CREB activation and annexin 1 expression in CCRF-CEM lymphoblastic cells: evidence for the involvement of cAMP and p38 MAPK - Download this document for free, or read online. Document in PDF available to download.

Mediators of Inflammation - Volume 12 2003, Issue 6, Pages 329-337



Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-517, Portugal

Faculty of Pharmacy, University of Coimbra, Portugal



Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims: Annexin 1 ANXA1, a member of the annexin family of calcium-binding and phospholipid-binding proteins, is a key mediator of the anti-inflammatory actions of steroid hormones. We have previously demonstrated that, in the human lymphoblastic CCRF-CEM cell line, both the synthetic glucocorticoid hormone, dexamethasone Dex, and the estrogen hormone, 17β-estradiol E2β, induce the synthesis of ANXA1, by a mechanism independent of the activation of their nuclear receptors. Recently, it was reported that the gene coding for ANXA1 contains a cAMP-responsive element CRE. In this work, we investigated whether Dex and E2β were able to induce the activation of CRE binding proteins CREB in the CCRF-CEM cells. Moreover, we studied the intracellular signalling pathways involved in CREB activation and ANXA1 synthesis in response to Dex and E2β; namely, the role of cAMP and the p38 mitogen-activated protein kinase MAPK.

Results: The results show that Dex and E2β were as effective as the cAMP analogue, dBcAMP, in inducing CREB activation. On the other hand, dBcAMP induced ANXA1 synthesis as effectively as these steroid hormones. Furthermore, the cAMP antagonist, Rp-8-Br-cAMPS, and the specific p38 MAPK inhibitor, SB203580, effectively prevented Dex-induced, E2β-induced and dBcAMP-induced CREB activation and ANXA1 synthesis.

Conclusions: Taken together, our results suggest that, in CCRF-CEM cells, Dex-induced and E2β-induced ANXA1 expression requires the activation of the transcription factor CREB, which in turn seems to be mediated by cAMP and the p38 MAPK. These findings also suggest that, besides the nuclear steroid hormone receptors, other transcription factors, namely CREB, may play important roles in mediating the anti-inflammatory actions of glucocorticoids and oestrogen hormones.





Author: M. Castro-caldas, A. F. Mendes, C. B. Duarte, and M. C. F. Lopes

Source: https://www.hindawi.com/



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