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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Yoshitaka Kawa, Tatsuya Nagano, Asuka Yoshizaki, Ryota Dokuni, Masahiro Katsurada, Tomomi Terashita, Yuichiro Yasuda, Kanoko Umezawa, Masatsugu Yamamoto, Hiroshi Kamiryo, Kazuyuki Kobayashi, Yoshihiro Nishimura
• Journal: PloS one (PLoS One) Vol. 13 Issue 9 Pg. e0203211 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30192865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ADRB2 protein, human
• Anti-Inflammatory Agents
• CCL20 protein, human
• Chemokine CCL20
• Lysophospholipids
• PTGER4 protein, human
• Receptors, Adrenergic, beta-2
• Receptors, Lysosphingolipid
• Receptors, Prostaglandin E, EP4 Subtype
• S1pr1 protein, mouse
• S1pr3 protein, mouse
• Sphingosine-1-Phosphate Receptors
• VPC23019
• sphingosine-1-phosphate receptor-3, human
• Phosphoserine
• sphingosine 1-phosphate
• Sphingosine

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Asthma (drug therapy, genetics, metabolism)
• Bronchi (immunology, metabolism, pathology)
• Cell Line
• Chemokine CCL20 (metabolism)
• Disease Models, Animal
• Eosinophilia (drug therapy, pathology)
• Epithelial Cells (immunology, metabolism, pathology)
• Female
• Gene Expression
• Gene Knockdown Techniques
• Humans
• Lysophospholipids (metabolism)
• Mice
• Mice, Inbred BALB C
• Phosphoserine (analogs & derivatives, pharmacology)
• Receptors, Adrenergic, beta-2 (genetics)
• Receptors, Lysosphingolipid (antagonists & inhibitors, genetics, metabolism)
• Receptors, Prostaglandin E, EP4 Subtype (genetics)
• Sphingosine (analogs & derivatives, metabolism)
• Sphingosine-1-Phosphate Receptors