Sphingosine 1-phosphate regulates IL-8 expression and secretion via S1PR1 and S1PR2 receptors-mediated signaling in extravillous trophoblast derived HTR-8/SVneo cells.
Placenta
; 36(10): 1115-21, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26321412
ABSTRACT
INTRODUCTION:
Both villous and extravillous trophoblast (EVT) cells produce a wide range of cytokines and also respond to them in autocrine and paracrine manner. Deregulation of cytokine secretion may lead to various pathologic conditions including preeclampsia. IL-8, a pro-inflammatory cytokine, regulates various cellular functions such as neutrophil trafficking, cell adhesion, tumor growth and has a role in placental development. IL-8 also promotes trophoblast cell migration and invasion, and stimulates the secretion of progesterone. The induction and mechanism of IL-8 secretion by EVT is still unknown.METHODS:
IL-8 mRNA expression and secretion was determined using real-time PCR and ELISA respectively. To identify the mechanism of IL-8 expression and secretion, selective antagonists and agonist of S1P receptor subtypes, Rac1 and Rho-kinase inhibitors were used.RESULTS:
We found that S1P induces IL-8 gene expression and protein secretion in EVT derived HTR-8/SVneo cells but not in BeWo cells. SEW2781, the selective agonist of S1PR(1), induced IL-8 gene expression but not protein secretion. The specific S1PR(2) inhibitor JTE-013 could drastically inhibit IL-8 secretion. Furthermore, pre-treatment of cells with the selective S1PR(1)/S1PR(3) antagonist VPC23019 inhibited IL-8 secretion by â¼45%. Selective Rho-kinase inhibitor Y27632 and Rac1 inhibitor NSC23766 could block IL-8 secretion in these cells.DISCUSSION:
In this study, we could show for the first time that S1P induces IL-8 mRNA expression and protein secretion in EVT cell line. S1P-induced IL-8 gene expression is mainly regulated via S1PR(1) and its secretion is regulated through S1PR(2) receptor subtype. Rho GTPases signaling is essential for S1P-induced IL-8 secretion.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esfingosina
/
Trofoblastos
/
Lisofosfolipídeos
/
Interleucina-8
/
Receptores de Lisoesfingolipídeo
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Placenta
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS