title: Sphingosine 1-phosphate (S1P) induced interleukin-8 (IL-8) release is mediated by S1P receptor 2 and nuclear factor κB in BEAS-2B cells.
abstract: 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.
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University and McGill University Health Centre Research Institute, Montréal, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Sullivan
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University and McGill University Health Centre Research Institute, Montréal, Canada.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Hirota
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University and McGill University Health Centre Research Institute, Montréal, Canada.
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016209:Interleukin-8; D008246:Lysophospholipids; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; C512478:EGFR protein, human; D066246:ErbB Receptors; D013110:Sphingosine
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