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

Sphingosine 1-phosphate (S1P) induced interleukin-8 (IL-8) release is mediated by S1P receptor 2 and nuclear factor κB in BEAS-2B cells.
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DOI:
10.1371/journal.pone.0095566
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Martin JG
Martin JG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
O'Sullivan MJ;Hirota N;Martin JG

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哮喘患者呼吸道上皮细胞可释放促炎细胞因子和趋化因子。1-磷酸鞘氨醇(S1P)是一种生物活性脂质,在哮喘患者的呼吸道中增加,可能会触发上皮细胞释放强大的中性粒细胞趋化因子白介素8(IL-8)。S1P是5G蛋白偶联受体S1PR1-5的配体。我们希望从受体(S)及其下游信号事件方面探讨S1P诱导IL-8分泌的机制。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)和活性氧物种(ROS)参与了其他G蛋白偶联受体激活后的IL-8释放,我们研究了它们在S1P诱导的IL-8释放中的重要性,并发现它们没有参与。这项研究揭示了S1PR2和NF-κB是治疗中性粒细胞呼吸道疾病(如严重哮喘)的潜在靶点。
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.
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