Activation of natural killer T cells contributes to Th1 bias in the murine liver after 14 d of ethinylestradiol exposure.
World J Gastroenterol
; 28(26): 3150-3163, 2022 Jul 14.
Article
en En
| MEDLINE
| ID: mdl-36051344
ABSTRACT
BACKGROUND:
As the main component of oral contraceptives (OCs), ethinylestradiol (EE) has been widely applied as a model drug to induce murine intrahepatic cholestasis. The clinical counterpart of EE-induced cholestasis includes women who are taking OCs, sex hormone replacement therapy, and susceptible pregnant women. Taking intrahepatic cholestasis of pregnancy (ICP) as an example, ICP consumes the medical system due to its high-risk fetal burden and the impotency of ursodeoxycholic acid in reducing adverse perinatal outcomes.AIM:
To explore the mechanisms and therapeutic strategies of EE-induced cholestasis based on the liver immune microenvironment.METHODS:
Male C57BL/6J mice or invariant natural killer T (iNKT) cell deficiency (Jα18-/- mice) were administered with EE (10 mg/kg, subcutaneous) for 14 d.RESULTS:
Both Th1 and Th2 cytokines produced by NKT cells increased in the liver skewing toward a Th1 bias. The expression of the chemokine/chemokine receptor Cxcr6/Cxcl16, toll-like receptors, Ras/Rad, and PI3K/Bad signaling was upregulated after EE administration. EE also influenced bile acid synthase Cyp7a1, Cyp8b1, and tight junctions ZO-1 and Occludin, which might be associated with EE-induced cholestasis. iNKT cell deficiency (Jα18-/- mice) robustly alleviated cholestatic liver damage and lowered the expression of the abovementioned signaling pathways.CONCLUSION:
Hepatic NKT cells play a pathogenic role in EE-induced intrahepatic cholestasis. Our research improves the understanding of intrahepatic cholestasis by revealing the hepatic immune microenvironment and also provides a potential clinical treatment by regulating iNKT cells.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colestasis
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Colestasis Intrahepática
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Células T Asesinas Naturales
Límite:
Animals
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
World J Gastroenterol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China