Sphingosylphosphorylcholine acts in an anti-inflammatory manner in renal mesangial cells by reducing interleukin-1beta-induced prostaglandin E2 formation

Xin, Cuiyan; Ren, Shuyu; Eberhardt, Wolfgang; Pfeilschifter, Josef; Huwiler, Andrea (2007). Sphingosylphosphorylcholine acts in an anti-inflammatory manner in renal mesangial cells by reducing interleukin-1beta-induced prostaglandin E2 formation. Journal of lipid research, 48(9), pp. 1985-96. Bethesda, Md.: American Society for Biochemistry and Molecular Biology ASBMB 10.1194/jlr.M700077-JLR200

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Sphingosylphosphorylcholine (SPC) is a bioactive lipid that binds to G protein-coupled-receptors and activates various signaling cascades. Here, we show that in renal mesangial cells, SPC not only activates various protein kinase cascades but also activates Smad proteins, which are classical members of the transforming growth factor-beta (TGFbeta) signaling pathway. Consequently, SPC is able to mimic TGFbeta-mediated cell responses, such as an anti-inflammatory and a profibrotic response. Interleukin-1beta-stimulated prostaglandin E(2) formation is dose-dependently suppressed by SPC, which is paralleled by reduced secretory phospholipase A(2) (sPLA(2)) protein expression and activity. This effect is due to a reduction of sPLA(2) mRNA expression caused by inhibited sPLA(2) promoter activity. Furthermore, SPC upregulates the profibrotic connective tissue growth factor (CTGF) protein and mRNA expression. Blocking TGFbeta signaling by a TGFbeta receptor kinase inhibitor causes an inhibition of SPC-stimulated Smad activation and reverses both the negative effect of SPC on sPLA(2) expression and the positive effect on CTGF expression. In summary, our data show that SPC, by mimicking TGFbeta, leads to a suppression of proinflammatory mediator production and stimulates a profibrotic cell response that is often the end point of an anti-inflammatory reaction. Thus, targeting SPC receptors may represent a novel therapeutic strategy to cope with inflammatory diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Xin, Cuiyan; Ren, Shuyu and Huwiler, Andrea

ISSN:

0022-2275

ISBN:

17592175

Publisher:

American Society for Biochemistry and Molecular Biology ASBMB

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:54

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1194/jlr.M700077-JLR200

PubMed ID:

17592175

Web of Science ID:

000248792100009

URI:

https://boris.unibe.ch/id/eprint/23004 (FactScience: 38533)

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