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

Abstract

BackgroundSphingosine 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.MethodsThe 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.ResultsS1P 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.ConclusionsS1P/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.

Propionate and Butyrate Produced by Gut Microbiota after Probiotic Supplementation Attenuate Lung Metastasis of Melanoma Cells in Mice

“…[ 35 ] In our experiments, we found that the expression of CCL20 in the lungs was increased significantly in the presence of propionate and butyrate, and the increased expression of CCL20 in the lungs was responsible for the recruitment of Th17 cells. Although several types of cells, including endothelial cells, epithelia cells, macrophages, and tumor cells in lungs may secrete CCL20, [ 36,38,42 ] we found that endothelial cells were the main contributors of CCL20 production. Some other tissues, such as liver and kidney, also expressed CCL20, while the expression did not increase under the same conditions.…”

“…The above results indicated that propionate and butyrate treatment promoted the recruitment of Th17 cells and CCL20 expression in the lungs. Previous studies reported that several types of cells in the lungs could secret CCL20, for example, endothelial cells, [ 36,37 ] epithelial cells, [ 38,39 ] macrophages, [ 40 ] and tumor cells. [ 41,42 ] To investigate which type of cell secrets CCL20, the endothelial cell line MS1, epithelial cell line MLE12, macrophage cell line Raw264.7, and B16F10 tumor cells were used.…”

The lncRNA H19/miR-766-3p/S1PR3 Axis Contributes to the Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis via the AKT/mTOR Pathway

“…Next, TargetScan, miRBase and miRTarBase were applied to predict the potential target genes of miR-766-3p ( Figure 4(a) ). We found 28 potential target genes and selected S1PR3, which is associated with the Ras/pERK and PI3K/AKT pathways [ 24 , 25 ] reported in psoriasis and plays role in pro-inflammatory cytokine regulation [ 26 ]. We found that expression of S1PR3 was downregulated in psoriasis tissue (Figures 4(b) and 4(c) ).…”

Chitinase-like protein YKL-40 regulates human bronchial epithelial cells proliferation, apoptosis, and migration through TGF-β1/Smads pathway

“…According to previous reports, 16,17 human bronchial epithelial cell line (BEAS-2B) was purchased from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China) and cultured in Roswell Park Memorial Institute (RPMI)-1640 medium (Gibco, Rockville, Maryland, USA) supplemented with 10% fetal bovine serum (Sigma-Aldrich, St. Louis, Missouri, USA) at 37 C in a 5% CO 2 incubator (Thermo Fisher Scientific, Waltham, Massachusetts, USA). Cells were treated as shown in Table 1.…”