Sphingolipids as Mediators of Inflammation and Novel Therapeutic Target in Inflammatory Bowel Disease

Olga Sukocheva, Elena Lukina, Eileen McGowan, Anupam Bishayee

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Morbidity of inflammatory gastrointestinal (GI) diseases continues to grow resulting in worsen quality of life and increased burden on public medical systems. Complex and heterogenous illnesses, inflammatory bowel diseases (IBDs) encompass several inflammation -associated pathologies including Crohn's disease and ulcerative colitis. IBD is often initiated by a complex interplay between host genetic and environmental factors, lifestyle and diet, and intestinal bacterial components. IBD inflammatory signature was linked to the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) signaling pathway that is currently targeted by IBD therapies. Sphingolipid signaling was identified as one of the key mediators and regulators of pro-inflammatory conditions, and, specifically, TNF-α related signaling. All GI tissues and circulating immune/blood cells contain activated sphingolipid-metabolizing enzymes, including sphingosine kinases (SphK1 and SphK2) that generate sphingosine-1-phosphate (S1P), a bioactive lipid and ligand for five G-protein coupled membrane S1P receptors (S1PRs). Numerous normal and pathogenic inflammatory responses are mediated by SphK/S1P/S1PRs signaling axis including lymphocyte trafficking and activation of cytokine signaling machinery. SphK1/S1P/S1PRs axis has recently been defined as a target for the treatment of GI diseases including IBD/colitis. Several SphK1 inhibitors and S1PRs antagonists have been developed as novel anti-inflammatory agents. In this review, we discuss the mechanisms of SphK/S1P signaling in inflammation-linked GI disorders. The potential role of SphK/S1PRs inhibitors in the prevention and treatment of IBD/colitis is critically evaluated.
Original languageEnglish
Title of host publicationAdvances in Protein Chemistry and Structural Biology
EditorsRossen Donev
Place of PublicationUSA
Pages123-158
Number of pages36
Volume120
DOIs
Publication statusPublished - Feb 2020

Publication series

NameAdvances in Protein Chemistry and Structural Biology
Volume120
ISSN (Print)1876-1623
ISSN (Electronic)1876-1631

Keywords

  • Fingolimod
  • FTY720
  • Inflammatory bowel disease
  • Sphingosine kinase
  • Sphingosine-1-phosphate
  • Sphingosine-1-phosphate receptor
  • Ulcerative colitis

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  • Cite this

    Sukocheva, O., Lukina, E., McGowan, E., & Bishayee, A. (2020). Sphingolipids as Mediators of Inflammation and Novel Therapeutic Target in Inflammatory Bowel Disease. In R. Donev (Ed.), Advances in Protein Chemistry and Structural Biology (Vol. 120, pp. 123-158). (Advances in Protein Chemistry and Structural Biology; Vol. 120).. https://doi.org/10.1016/bs.apcsb.2019.11.003