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Eur J Immunol ; 53(4): e2250100, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36648433

RESUMEN

Autoimmune hepatitis (AIH) eventually progresses to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, causing irreversible damage to the liver. Concanavalin A-induced hepatitis in mice is a well-established model with pathophysiology similar to that of immune-mediated liver injury in human viral and autoimmune hepatitis, and it has been widely used to explore the pathogenesis and clinical treatment of human immune hepatitis. Artemisinin has been shown to exhibit anti-inflammatory effects through unclear mechanisms. In this study, we aimed to assess the effect of the artemisinin derivative TPN10466 on AIH. In vitro studies showed that TPN10466 dose dependently inhibited the percentage of IFN-γ-producing T cells. Further studies showed that TPN10466 attenuated the disease severity of AIH by downregulating the ability of lymphocytes to secrete IFN-γ and by reducing lymphocyte number in the liver. In addition, we found that TPN10466 treatment reduced T-cell responses by inhibiting JNK, ERK, and p38 pathways. In conclusion, our work suggests that TPN10466 provides protection against the autoimmune disease AIH by suppressing the inflammatory response of T cells, suggesting that TPN10466 may be a promising potential agent for the treatment of AIH.


Asunto(s)
Artemisininas , Hepatitis Autoinmune , Animales , Humanos , Ratones , Artemisininas/metabolismo , Artemisininas/farmacología , Artemisininas/uso terapéutico , Concanavalina A/metabolismo , Concanavalina A/farmacología , Concanavalina A/uso terapéutico , Hepatitis Autoinmune/tratamiento farmacológico , Hígado/patología , Sistema de Señalización de MAP Quinasas
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