Role of S1P/S1PR3 axis in release of CCL20 from human bronchial epithelial cells.

Role of S1P/S1PR3 axis in release of CCL20 from human bronchial epithelial cells.
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DOI:
10.1371/journal.pone.0203211
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Nishimura Y
Nishimura Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kawa Y;Nagano T;Yoshizaki A;Dokuni R;Katsurada M;Terashita T;Yasuda Y;Umezawa K;Yamamoto M;Kamiryo H;Kobayashi K;Nishimura Y

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Sphingosine kinase phosphorylates sphingosine to generate sphingosine 1 phosphate (S1P) following stimulation of the five plasma membrane G-protein-coupled receptors. The objective of this study is to clarify the role of S1P and its receptors (S1PRs), especially S1PR3 in airway epithelial cells. The effects of S1P on asthma-related genes expression were examined with the human bronchial epithelial cells BEAS-2B and Calu-3 using a transcriptome analysis and siRNA of S1PRs. To clarify the role of CCL20 in the airway inflammation, BALB/c mice were immunized with ovalbumin (OVA) and subsequently challenged with an OVA-containing aerosol to induce asthma with or without intraperitoneal administration of anti-CCL20. Finally, the anti-inflammatory effect of VPC 23019, S1PR1/3 antagonist, in the OVA-induced asthma was examined. S1P induced the expression of some asthma-related genes, such as ADRB2, PTGER4, and CCL20, in the bronchial epithelial cells. The knock-down of SIPR3 suppressed the expression of S1P-inducing CCL20. Anti-CCL20 antibody significantly attenuated the eosinophil numbers in the bronchoalveolar lavage fluid (P<0.01). Upon OVA challenge, VPC23019 exhibited substantially attenuated eosinophilic inflammation. S1P/S1PR3 pathways have a role in release of proinflammatory cytokines from bronchial epithelial cells. Our results suggest that S1P/S1PR3 may be a possible candidate for the treatment of bronchial asthma.
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