Sphingosine synergistically stimulates tumor necrosis factor alpha- induced prostaglandin E2 production in human fibroblasts

doi:10.1084/JEM.174.6.1363

Paper

Sphingosine synergistically stimulates tumor necrosis factor alpha- induced prostaglandin E2 production in human fibroblasts

Published Dec 1, 1991 · M. Candela, S. C. Barker, L. Ballou

The Journal of Experimental Medicine

Q1 SJR score

45

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

Sphingosine is a biologically active derivative of sphingomyelin. It affects diverse cellular functions and its mechanism(s) of action is poorly defined. Tumor necrosis factor alpha (TNF alpha) has recently been shown to rapidly induce sphingomyelin turnover, implicating this metabolic pathway in TNF alpha signal transduction. Because TNF alpha is known to induce prostaglandin E2 (PGE2) production in human fibroblasts, we tested the effect of sphingosine on TNF alpha-induced PGE2 production. We found that sphingosine enhanced TNF alpha-induced PGE2 production by as much as 18-fold over TNF alpha alone. Sphingosine appeared to stimulate TNF alpha-induced PGE2 production independent of TNF alpha-mediated interleukin 1 (IL-1) production, because anti-IL-1 antibodies and IL-1 receptor antagonist protein (IRAP) did not inhibit TNF alpha-induced PGE2 production or the stimulatory effect of sphingosine. TNF alpha stimulated PGE2 production to the same degree in normal and protein kinase C (PKC) downregulated cells in the presence and absence of sphingosine, indicating that neither TNF alpha nor sphingosine require active PKC to elicit their respective effects. The sphingosine analogues stearylamine and stearoyl-D-sphingosine had little or no effect on TNF alpha-mediated PGE2 production, supporting a specific role for sphingosine in the activation process. Short-term (1 min) exposure of cells to sphingosine dramatically increased TNF alpha- induced PGE2 production. A potential mechanism by which sphingosine could increase TNF alpha-induced PGE2 production involves enhancement of phospholipase A2 (PLA2) and/or cyclooxygenase (Cox) activity, the rate-limiting enzymes in PGE2 production. We found that both TNF alpha and sphingosine alone enhanced these enzymatic activities, and that sphingosine additively increased the effect of TNF alpha on phospholipase A2 activity. It appears that sphingosine affects TNF alpha-induced PGE2 production via a mechanism that is independent of PKC involvement, and that sphingosine may function as an endogenous second messenger capable of modulating the responsiveness of the cell to external stimuli.

In Vitro Study

Study Snapshot

Sphingosine enhances tumor necrosis factor alpha-induced prostaglandin E2 production in human fibroblasts by as much as 18-fold, potentially acting as an endogenous second messenger.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Sphingosine synergistically stimulates tumor necrosis factor alpha- induced prostaglandin E2 production in human fibroblasts

Sign up to use Study Snapshot

References

Tumor necrosis factor.

Understanding tumor necrosis factor is crucial for dermatologists as it plays a role in defense, homeostasis, and various disease states, with potential clinical uses and anti-tumor necrosis factor agents.

Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation.

Sphingomyelin turnover plays a key role in transducing the actions of TNF alpha and gamma-IFN on leukemia cell differentiation, with specific function in the monocytic pathway.

Sphingosine potentiates IL-1-mediated prostaglandin E2 production in human fibroblasts.

Sphingosine, a PKC inhibitor, can enhance IL-1-mediated prostaglandin E2 production in human fibroblasts by enhancing phospholipase A2 activity, resulting in increased availability of arachidonic acid for conversion to PGE2.

Increases in phosphatidic acid levels accompany sphingosine-stimulated proliferation of quiescent Swiss 3T3 cells.

Sphingosine stimulates Swiss 3T3 cell proliferation by increasing phosphatidic acid levels, mimicking its effects on signal transduction and cellular responses.

Bifunctional role of glycosphingolipids. Modulators for transmembrane signaling and mediators for cellular interactions.

Glycosphingolipids at the cell surface modulate transmembrane signaling and play a key role in specific cell recognition, independent of fibronectin/integrin or surface lectin systems.

Citations

Sphingosine 1-Phosphate Induces Cyclooxygenase-2/Prostaglandin E2 Expression via PKCα-dependent Mitogen-Activated Protein Kinases and NF-κB Cascade in Human Cardiac Fibroblasts

S1P induces COX-2 expression and PGE2 production in human cardiac fibroblasts through PKC-mediated MAPK cascades, potentially offering rational therapeutic interventions for heart injury or inflammation.

Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts

Ranibizumab reduces tissue scarring and wound healing by regulating the expression of fibrotic-associated metabolites, particularly vitamin Bs, in human Tenon's fibroblasts.

Intraplantar‐injected ceramide in rats induces hyperalgesia through an NF‐κB‐ and p38 kinase‐dependent cyclooxygenase 2/prostaglandin E2 pathway

Intraplantar injection of ceramide in rats induces thermal hyperalgesia through an NFB and p38 kinase-dependent pathway, offering potential for developing novel analgesics.

Royal jelly enhances migration of human dermal fibroblasts and alters the levels of cholesterol and sphinganine in an in vitro wound healing model

Royal jelly enhances fibroblast migration and alters lipid levels, potentially promoting wound healing in normal skin cells.

Mesenchymal Stem Cells Inhibit Human Th17 Cell Differentiation and Function and Induce a T Regulatory Cell Phenotype

Mesenchymal stem cells can inhibit human Th17 cell differentiation and function by inducing a T cell regulatory phenotype, potentially offering anti-inflammatory benefits.