TY  - JOUR
A1  - Xin, Cuiyan
A1  - Ren, Shuyu
A1  - Eberhardt, Wolfgang
A1  - Pfeilschifter, Josef
A1  - Huwiler, Andrea
T1  - Sphingosylphosphorylcholine acts in an anti-inflammatory manner in renal mesangial cells by reducing interleukin-1β-induced prostaglandin E2 formation
T2  - Journal of lipid research
N2  - 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-β (TGFβ) signaling pathway. Consequently, SPC is able to mimic TGFβ-mediated cell responses, such as an anti-inflammatory and a profibrotic response. Interleukin-1β-stimulated prostaglandin E2 formation is dose-dependently suppressed by SPC, which is paralleled by reduced secretory phospholipase A2 (sPLA2) protein expression and activity. This effect is due to a reduction of sPLA2 mRNA expression caused by inhibited sPLA2 promoter activity. Furthermore, SPC upregulates the profibrotic connective tissue growth factor (CTGF) protein and mRNA expression. Blocking TGFβ signaling by a TGFβ receptor kinase inhibitor causes an inhibition of SPC-stimulated Smad activation and reverses both the negative effect of SPC on sPLA2 expression and the positive effect on CTGF expression. In summary, our data show that SPC, by mimicking TGFβ, 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.
KW  - transforming growth factor-β
KW  - Smad
KW  - secretory phospholipase A
KW  - connective tissue growth factor
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76287
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-762873
SN  - 0022-2275
VL  - 48.2007
IS  - 9
SP  - 1985
EP  - 1996
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -