Sphingosine 1-phosphate (S1P) induced interleukin-8 (IL-8) release is mediated by S1P receptor 2 and nuclear factor κB in BEAS-2B cells

• Published in: PloS one 2014-04, Vol.9 (4), p.e95566-e95566
• Main Authors: O'Sullivan, Michael J, Hirota, Nobuaki, Martin, James G
• Format: Article
• Language: English
• Subjects: Asthma; Biology and Life Sciences; Cell Line; Chemokines; Cytokines; Downstream effects; Epidermal growth factor; Epidermal growth factor receptors; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium; G protein-coupled receptors; Humans; Inflammation; Interleukin; Interleukin 8; Interleukin-8 - metabolism; Kinases; Laboratories; Leukocytes (neutrophilic); Lysophospholipids - pharmacology; Medicine and Health Sciences; Neutrophils; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Oxygen; Pathogenesis; Penicillin; Phosphates; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptor, Epidermal Growth Factor - metabolism; Receptors; Receptors, Lysosphingolipid - metabolism; Respiratory tract diseases; Rodents; Signaling; Smooth muscle; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Sphingosine 1-phosphate
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095566

The airway epithelium may release pro-inflammatory cytokines and chemokines in the asthmatic airway. Sphingosine 1-phosphate (S1P) is a bioactive lipid, increased in the airways of asthmatics, that may trigger the release of the potent neutrophil chemoattractant Interleukin-8 (IL-8) by epithelial cells. S1P is a ligand for 5 G protein-coupled receptors, S1PR1-5. We wished to explore the mechanisms of S1P induced IL-8 secretion with regard to the receptor(s) and downstream signaling events involved. Our results indicate that S1P induced IL-8 release is mediated by S1PR2 and the transcription factor NF-κB. Since the Epidermal Growth Factor Receptor (EGFR) and reactive oxygen species (ROS) have been implicated in IL-8 release in response to activation of other G protein-coupled receptors, we examined their importance in S1P induced IL-8 release and established that they are not involved. This study reveals S1PR2 and NF-κB as potential therapeutic targets in neutrophilic airway diseases such as severe asthma.