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- W2935390400 endingPage "1051" @default.
- W2935390400 startingPage "1038" @default.
- W2935390400 abstract "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 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." @default.
- W2935390400 created "2019-04-11" @default.
- W2935390400 creator A5008663814 @default.
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- W2935390400 creator A5066955374 @default.
- W2935390400 creator A5071822561 @default.
- W2935390400 creator A5083823979 @default.
- W2935390400 date "2019-04-26" @default.
- W2935390400 modified "2023-10-01" @default.
- W2935390400 title "Inhibition of the sphingosine‐1‐phosphate pathway promotes the resolution of neutrophilic inflammation" @default.
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