O'Sullivan Michael J, Hirota Nobuaki, Martin James G
Meakins-Christie Laboratories, Department of Medicine, McGill University and McGill University Health Centre Research Institute, Montréal, Canada.
PLoS One. 2014 Apr 17;9(4):e95566. doi: 10.1371/journal.pone.0095566. eCollection 2014.
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.
气道上皮可能在哮喘气道中释放促炎细胞因子和趋化因子。鞘氨醇-1-磷酸（S1P）是一种生物活性脂质，在哮喘患者的气道中含量增加，它可能会触发上皮细胞释放强效中性粒细胞趋化因子白细胞介素-8（IL-8）。S1P是5种G蛋白偶联受体S1PR1 - 5的配体。我们希望探讨S1P诱导IL-8分泌的机制，涉及相关受体和下游信号事件。我们的结果表明，S1P诱导的IL-8释放是由S1PR2和转录因子NF-κB介导的。由于表皮生长因子受体（EGFR）和活性氧（ROS）已被证明与其他G蛋白偶联受体激活后IL-8的释放有关，我们研究了它们在S1P诱导的IL-8释放中的重要性，并确定它们不参与其中。这项研究揭示了S1PR2和NF-κB作为嗜中性气道疾病（如重度哮喘）潜在的治疗靶点。
