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

Abstract

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-b (TGFb) signaling pathway. Consequently, SPC is able to mimic TGFbmediated cell responses, such as an anti-inflammatory and a profibrotic response. Interleukin-1b-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 TGFb signaling by a TGFb receptor kinase inhibitor causes an inhibition of SPCstimulated 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 TGFb, 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.-Xin, C., S. Ren, W. Eberhardt, J. Pfeilschifter, and A. Huwiler. Sphingosylphosphorylcholine acts in an antiinflammatory manner in renal mesangial cells by reducing interleukin-1b-induced prostaglandin E 2 formation.

Antioxidant and renoprotective effects of sphingosylphosphorylcholine on contrast-induced nephropathy in rats

“…42,43 Another study showed that SPC activates the transforming growth factor b/Smad signaling cascade and, thereby, is able to reduce the promoter activity and expression of pro-inflammatory enzymes like secretory phospholipase A2 and iNOS in renal mesangial cells. 44 SPC is probably due to its activity in reducing iNOS to keep NO levels within physiological limits. Positive effects of SPC kept NO levels in physiologic limits so that vascular permeability is kept within normal limits.…”

Effects of sphingosylphosphorylcholine against oxidative stress and acute lung ınjury ınduced by pulmonary contusion in rats

“…Sphingosylphosphorylcholine exerts most of its action by binding to and activating cell surface receptors, thereby triggering various cell responses such as vasoconstriction or dilation, angiogenesis, stress fiber formation, and cytoskeletal rearrangements [37,38]. Another study showed that SPC activates the transforming growth factor β/Smad signaling cascade and, thereby, is able to reduce the promoter activity and expression of pro-inflammatory enzymes like secretory phospholipase A2 and iNOS in renal mesangial cells [39]. In the present study, SPC reduced pulmonary injury owing to pulmonary contusion through its anti-inflammatory effect.…”

Adverse effects of high glucose and free fatty acid on cardiomyocytes are mediated by connective tissue growth factor

“…Cardiac hypertrophy at a cell level can be characterized by an increase in cell size or protein to cell in cardiac myocyte area (24,31). Recent studies have identified markers of pathological cardiac hypertrophy, with "fetalization" of the cardiac myocytes and expression of genes such atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), ␣-skeletal actin (␣-SKA), and ␤-myosin heavy chain (␤-MHC) (4,20,35,53).…”