Sphingosine-1-phosphate in chronic intestinal inflammation and cancer

摘要: Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, and the kinase that produces it have now emerged as key regulators of numerous cellular processes involved in inflammation cancer. Here, we review importance S1P colitis colitis-associated cancer (CAC) discuss our recent work demonstrating produced by upregulation SphK1 during associated is essential for production multifunctional NF-κB-regulated cytokine IL-6, persistent activation transcription factor Stat3, consequent receptor, S1PR1. The effectiveness pro-drug FTY720 (known fingolimod), approved treatment multiple sclerosis, has become gold standard S1P-centric drugs, will be used to illustrate therapeutic value modulating receptor functions. We results showing FTY720/fingolimod administration interferes with SphK1/S1P/S1PR1 axis suppresses NF-κB/IL-6/Stat3 malicious amplification loop CAC. These preclinical studies suggest may useful treating colon individuals ulcerative colitis.