Involvement of the ABC-transporter ABCC1 and the sphingosine 1-phosphate receptor subtype S1P(3) in the cytoprotection of human fibroblasts by the glucocorticoid dexamethasone

Nieuwenhuis, Barbara; Lüth, Anja; Chun, Jerold; Huwiler, Andrea; Pfeilschifter, Josef; Schäfer-Korting, Monika; Kleuser, Burkhard (2009). Involvement of the ABC-transporter ABCC1 and the sphingosine 1-phosphate receptor subtype S1P(3) in the cytoprotection of human fibroblasts by the glucocorticoid dexamethasone. International journal of molecular medicine, 87(6), pp. 645-57. Athens: Spandidos Publications 10.1007/s00109-009-0468-x

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Glucocorticoids (GC) represent the most commonly used drugs for the treatment of acute and chronic inflammatory skin diseases. However, the topical long-term therapy of GC is limited by the occurrence of skin atrophy. Most interestingly, although GC inhibit proliferation of human fibroblasts, they exert a pronounced anti-apoptopic action. In the present study, we further elucidated the molecular mechanism of the GC dexamethasone (Dex) to protect human fibroblasts from programmed cell death. Dex not only significantly alters the expression of the cytosolic isoenzyme sphingosine kinase 1 but also initiated an enhanced intracellular formation of the sphingolipid sphingosine 1-phosphate (S1P). Investigations using S1P (3) ((-/-)) -fibroblasts revealed that this S1P-receptor subtype is essential for the Dex-induced cytoprotection. Moreover, we demonstrate that the ATP-binding cassette (ABC)-transporter ABCC1 is upregulated by Dex and may represent a crucial carrier to transport S1P from the cytosol to the S1P(3)-receptor subtype.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Huwiler, Andrea

ISSN:

1107-3756

Publisher:

Spandidos Publications

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:10

Last Modified:

04 May 2014 23:22

Publisher DOI:

10.1007/s00109-009-0468-x

PubMed ID:

19370318

Web of Science ID:

000266475800011

URI:

https://boris.unibe.ch/id/eprint/30676 (FactScience: 194940)

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