Journal
PHARMACOLOGICAL RESEARCH
Volume 61, Issue 5, Pages 449-459Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2009.12.005
Keywords
Glucocorticoids; Programmed cell death; Sphingosine 1-phosphate; S1P-receptors; Akt signalling; Bcl-2 family
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Topical used glucocorticoids (GC) represent an important class of steroid hormones for the treatment of a broad range of acute or chronical inflammatory diseases. Most interestingly, GC exert a pronounced antiapoptotic effect in primary human fibroblasts whereas in variety of hematopoietic cells a pro-apoptotic effect is visible. Recently, it has been discovered that in human fibroblasts the GC dexamethasone (Dex) exerts its protection from programmed cell death via the formation of the lipid mediator sphingosine 1-phosphate (SIP) followed by an activation of the S1P(3)-receptor subtype. In the present study, the molecular mechanism of Dex to protect human fibroblasts from apoptosis was elucidated. Thereupon, Dex not only mediates its anti-apoptotic effect via activation of phosphoinositide 3-kinase (PI3K)/Akt signalling but also includes an involvement of the Bcl-2 family protein Bcl(XL). Most interestingly, the use of S1P(3)-knockout fibroblasts revealed that the S1P(3)-receptor subtype is crucial for activation of PKB/Akt as well as Bcl(XL) by Dex. (C) 2009 Elsevier Ltd. All rights reserved.
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