Blocking sphingosine 1-phosphate receptor 1 with modulators reduces immune cells infiltration and alleviates endometriosis in mice.
Reprod Biomed Online
; 47(5): 103304, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37757611
ABSTRACT
RESEARCH QUESTION Do sphingosine 1-phosphate (S1P) modulators have therapeutic effects on endometriosis in mice and, if they do, which receptor is responsible for these effects? DESIGN:
A surgically induced endometriosis mouse model was established. In the pilot experiment, lesions were harvested to assess fibrosis and inflammation and determine the optimal concentration of a broad-spectrum S1P modulator, FTY720. Subsequently, FTY720 was compared with a selective S1P receptor 1 modulator, SEW2871 to evaluate their effects on endometriotic lesion growth, fibrosis, inflammation and immune cell infiltration.RESULTS:
The results demonstrated that both FTY720 and SEW2871, two S1P receptor modulators, effectively inhibited the growth and fibrosis of endometriotic lesions. SEW2871 inhibited inflammation-related cytokine expression, including PTGS-2, IL-1ß, TNF-α and TGF-ß1, more effectively compared with FTY720. Lymphopaenia was mainly caused by FTY720, whereas SEW2871 had a lesser effect. Both FTY720 and SEW2871 significantly reduced CD45+ cells (Pâ¯=â¯0.002 and Pâ¯=â¯0.032, respectively) and F4/80+ cells (P < 0.001 and Pâ¯=â¯0.004, respectively) infiltration into the lesions, with FTY720 exerting a strong regulatory effect on CD4+ T cells.CONCLUSIONS:
This study suggests that S1P receptor 1 could be investigated as a potential novel therapeutic target for endometriosis in the future.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endometriose
/
Cloridrato de Fingolimode
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Reprod Biomed Online
Ano de publicação:
2023
Tipo de documento:
Article