Baicalein upregulates macrophage TREM2 expression via TrKB-CREB1 pathway to attenuate acute inflammatory injury in acute-on-chronic liver failure.
Int Immunopharmacol
; 139: 112685, 2024 Sep 30.
Article
en En
| MEDLINE
| ID: mdl-39047449
ABSTRACT
OBJECTIVE:
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by a high short-term mortality rate, and effective interventions are still lacking. This study aims to investigate whether the small molecule baicalein can mitigate ACLF and elucidate the molecular mechanisms.METHODS:
The ACLF mouse model was induced through chronic liver injury using carbon tetrachloride, followed by acute inflammation induction with lipopolysaccharide (LPS). Baicalein was administered through intraperitoneal injection to explore its therapeutic effects. In vitro experiments utilized the iBMDM macrophage cell line to investigate the underlying mechanisms. Peripheral blood was collected from clinical ACLF patients for validation.RESULTS:
In the LPS-induced ACLF mouse model, baicalein demonstrated a significant reduction in acute inflammation and liver damage, as evidenced by histopathological evaluation, liver function analysis, and inflammatory marker measurements. Transcriptomic analysis, coupled with molecular biology experiments, uncovered that baicalein exerts its effects in ACLF by activating the TrKB-CREB1 signaling axis to upregulate the surface expression of the TREM2 receptor on macrophages. This promotes M2 macrophage polarization and activates efferocytosis, thereby inhibiting inflammation and alleviating liver damage. Furthermore, we observed a substantial negative correlation between postoperative peripheral blood plasma soluble TREM2 (sTREM2) levels and inflammation, as well as adverse outcomes in clinical ACLF patients.CONCLUSION:
Baicalein plays a protective role in ACLF by enhancing the surface expression of the TREM2 receptor on macrophages, leading to the suppression of inflammation, mitigation of liver damage, and a reduction in mortality. Additionally, plasma sTREM2 emerges as a critical indicator for predicting adverse outcomes in ACLF patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
/
Receptores Inmunológicos
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Transducción de Señal
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Flavanonas
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Insuficiencia Hepática Crónica Agudizada
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Macrófagos
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Ratones Endogámicos C57BL
Límite:
Adult
/
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China