Suppression of Th17 cell differentiation via sphingosine-1-phosphate receptor 2 by cinnamaldehyde can ameliorate ulcerative colitis.
Biomed Pharmacother
; 134: 111116, 2021 Feb.
Article
en En
| MEDLINE
| ID: mdl-33341041
Ulcerative colitis (UC) is chronic disease characterized by diffuse inflammation of the mucosa of the colon and rectum. Although the etiology is unknown, dysregulation of the intestinal mucosal immune system is closely related to UC. Cinnamaldehyde (CA) is a major active compound from cinnamon, is known as its anti-inflammatory and antibacterial. However, little research focused on its regulatory function on immune cells in UC. Therefore, we set out to explore the modulating effects of CA on immune cells in UC. We found that CA reduced the progression of colitis through controlling the production of proinflammatory cytokines and inhibiting the proportion of Th17 cells. Furthermore, the liquid chromatography-mass spectrometry (LC-MS) method was employed for analyzing and differentiating metabolites, data showed that sphingolipid pathway has a great influence on the effect of CA on UC. Meanwhile, sphingosine-1-phosphate receptor 2 (S1P2) and Rho-GTP protein levels were downregulated in colonic tissues after CA treatment. Moreover, in vitro assays showed that CA inhibited Th17 cell differentiation and downregulated of S1P2 and Rho-GTP signaling. Notably, we found that treatment with S1P2 antagonist (JTE-013) weakened the inhibitory effect of CA on Th17 cells. Furthermore, S1P2 deficiency (S1P2-/-) blocked the effect of CA on Th17 cell differentiation. In addition, CA can also improve inflammation via lncRNA H19 and MIAT. To sum up, this study provides clear evidence that CA can ameliorate ulcerative colitis through suppressing Th17 cells via S1P2 pathway and regulating lncRNA H19 and MIAT, which further supports S1P2 as a potential drug target for immunity-mediated UC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acroleína
/
Colitis Ulcerosa
/
Diferenciación Celular
/
Colon
/
Receptores de Esfingosina-1-Fosfato
/
Mucosa Intestinal
/
Antiinflamatorios
Límite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Francia