S1P promotes inflammation-induced tube formation by HLECs via the S1PR1/NF-κB pathway.
Int Immunopharmacol
; 66: 224-235, 2019 Jan.
Article
em En
| MEDLINE
| ID: mdl-30476824
ABSTRACT
Inflammation-induced lymphangiogenesis is a widely accepted concept. However, most of the inflammatory factors and their related mechanisms have not been clarified. It has been reported that sphingosine-1-phosphate (S1P) is not only closely related to the chronic inflammatory process but also affects angiogenesis. Therefore, we investigated the inflammatory effects of S1P on human lymphatic endothelial cells (HLECs). Our results showed that S1P promotes tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) secretion in HLECs. We also confirmed that S1P-stimulated TNF-α and IL-1ß secretion is mediated through S1P receptor 1 (S1PR1). Using TNF-α siRNA and IL-1ß siRNA, we found that TNF-α and IL-1ß play essential roles in S1P-induced HLEC proliferation, migration, and tube formation. S1P induces phosphorylation of NF-κB p65 and activation of NF-κB nuclear translocation. A S1PR1 antagonist (W146) and NF-κB inhibitor (BAY11-7082) inhibited S1P-induced TNF-α and IL-1ß secretion and prevented NF-κB nuclear translocation. Taken together, the results demonstrated for the first time that S1P promotes the secretion of TNF-α and IL-1ß in HLECs via S1PR1-mediated NF-κB signaling pathways, thus affecting lymphangiogenesis. The study provides a new strategy for finding treatments for lymphangiogenesis-related diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Organogênese
/
Células Endoteliais
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Linfangiogênese
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Receptores de Lisoesfingolipídeo
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Inflamação
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China