Inhibition of the sphingosine-1-phosphate pathway promotes the resolution of neutrophilic inflammation.

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "Inhibition of the sphingosine-1-phosphate pathway promotes the resolution of neutrophilic inflammation."

Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution phase of inflammation is unknown. Here, we investigated the effects of inhibition of S1P receptors and the blockade of S1P synthesis in BALB/c mice and human neutrophils. S1P and S1PR1-3 receptors expression were increased in cells from the pleural cavity stimulated with lipopolysaccharide (LPS). Using different antagonists of S1PRs and inhibitors of different steps of the metabolic pathway of S1P production, we show that S1P and its receptors are involved in regulating neutrophil survival and resolution of inflammation in the pleural cavity. Given the role of the S1P-S1PR axis in resolution of inflammation, we sought to identify whether blockade at different levels of the sphingosine-1-phosphate synthesis pathway could affect neutrophil survival in vitro. Inhibitors of the S1P pathway were also able to induce human neutrophil apoptosis. In addition, blockade of S1P synthesis or its receptor facilitated the efferocytosis of apoptotic neutrophil. Taken together, our data demonstrate a fundamental role for S1P in regulating the outcome of inflammatory responses, and position S1P-S1PR axis as a potential target for treatment of neutrophilic inflammation. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: European journal of immunology
ISSN: 1521-4141


DeepDyve research library

PubMed Articles [18549 Associated PubMed Articles listed on BioPortfolio]

Sphingosine 1-phosphate promotes mesenchymal stem cell-mediated cardioprotection against myocardial infarction via ERK1/2-MMP-9 and Akt signaling axis.

The sphingolipid metabolite sphingosine 1‑phosphate (S1P) has emerged as a potential cardioprotective molecule against ischemic heart disease. Moreover, S1P triggers mobilization and homing of bone ...

Sphingosine-1-phosphate Signaling Modulates Terminal Erythroid Differentiation through the Regulation of Mitophagy.

Erythropoiesis is a highly-coordinated stepwise process involving the progressive clearance of mitochondria via mitophagy. Based on the expression of several macroautophagy and mitophagy specific gene...

Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis.

Sphingolipid metabolism plays an important role in determining the fate of a cell. Among several sphingolipid metabolites, ceramide is a key player in intracellular signal transduction. Ceramide is us...

CD40 Enhances Sphingolipids in Orbital Fibroblasts: Potential Role of Sphingosine-1-Phosphate in Inflammatory T-Cell Migration in Graves' Orbitopathy.

Graves' orbitopathy (GO) is an autoimmune orbital disorder associated with Graves' disease caused by thyrotropin receptor autoantibodies. Orbital fibroblasts (OFs) and CD40 play a key role in disease ...

Deficiency of Sphingosine-1-Phosphate Receptor 2 (S1P) Attenuates Bleomycin-Induced Pulmonary Fibrosis.

Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although ...

Clinical Trials [5773 Associated Clinical Trials listed on BioPortfolio]

Anti-Inflammatory Pulmonal Therapy of CF-Patients With Amitriptyline and Placebo

Our data indicate that the CFTR-molecule functions as a transporter for sphingosine-1-phosphate and sphingosine or regulates the uptake of these sphingolipids by epithelial cells. The dist...

Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia

This phase II trial studies how well ruxolitinib phosphate works in treating patients with chronic neutrophilic leukemia (CNL) or atypical chronic myeloid leukemia (aCML). Ruxolitinib phos...

Non-Eosinophilic Neutrophilic Asthma

Define and characterize the neutrophilic phenotype of severe asthma.

Ketamine's Efficiency in the Treatment of Chronic Pain: Kynurenin Pathway

The kynurenine pathway is involved in hyperalgesia. This pathway is activated by inflammation. Ketamine would interact with the kynurenine pathway and inflammation. Our working hypotheses ...

INvestigating COPD Outcomes, Genomics and Neutrophilic Inflammation With Tiotropium and Olodaterol

This protocol describes a randomised controlled trial to test the hypothesis that 6 months of treatment with tiotropium and olodaterol will result in a reduction in bacterial load, an impr...

Medical and Biotech [MESH] Definitions

A subfamily of lysophospholipid receptors with specificity for LYSOSPHINGOLIPIDS such as sphingosine-1-phosphate and sphingosine phosphorylcholine.

A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS.

An enzyme of the transferase class that catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC

An enzyme of the transferase class that catalyzes the reaction sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to yield D-erythrose 4-phosphate and D-fructose phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC

An oxidative decarboxylation process that converts GLUCOSE-6-PHOSPHATE to D-ribose-5-phosphate via 6-phosphogluconate. The pentose product is used in the biosynthesis of NUCLEIC ACIDS. The generated energy is stored in the form of NADPH. This pathway is prominent in tissues which are active in the synthesis of FATTY ACIDS and STEROIDS.

Quick Search


DeepDyve research library

Relevant Topic

Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Searches Linking to this Article