S100A9 regulates M1 macrophage polarization and exacerbates steatotic liver ischemia-reperfusion injury.
Transpl Immunol
; : 102134, 2024 Oct 03.
Article
en En
| MEDLINE
| ID: mdl-39368753
ABSTRACT
OBJECTIVE:
Steatotic livers exhibit higher susceptibility to ischemia reperfusion (IR) injury, which increase the risk of primary graft non-function following liver transplantation. S100A9 is identified as a pivotal innate immune sensor that regulates the progression of liver diseases. However, its significance in steatotic liver IR injury remains under-investigated.METHODS:
In mice model, we generated S100A9 knockout (S100A9 KO) mice to investigate the role of S100A9 in IR-stimulated steatotic livers. In vitro, primary bone marrow-derived macrophages were utilized to explore the effect of S100A9 in regulating macrophage polarization and inflammation.RESULTS:
S100A9 expression was markedly increased in steatotic livers of mice subjected to IR insult. S100A9 deletion significantly attenuated liver inflammatory injury, as evidenced by the diminished infiltration of both monocytes/macrophages and neutrophils (pâ¯<â¯0.05). The expression of proinflammatory factors was reduced (pâ¯<â¯0.05) at the same time. Additionally, S100A9-deficient livers demonstrated M1 polarization decrease and Toll-like receptor 4 (TLR4) suppression (pâ¯<â¯0.05). In vitro, genetic TLR4 inhibition led to nuclear factor kappa B (NF-κB) inactivation and subsequent M1 polarization decrease (pâ¯<â¯0.05) in macrophages treated with recombinant S100A9. Conclusion In this study, we highlight the pivotal role of TLR4/NF-κB as a critical mediator of S100A9 in inducing M1 macrophage polorization- dependent inflammation in steatotic livers IR injury.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Transpl Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
TRANSPLANTE
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos