The role of lipoproteinassociated phospholipase A2 in inflammatory response and macrophage infiltration in sepsis and the regulatory mechanisms.
Funct Integr Genomics
; 24(5): 178, 2024 Sep 30.
Article
en En
| MEDLINE
| ID: mdl-39343830
ABSTRACT
Lipoproteinassociated phospholipase A2 (Lp-PLA2), encoded by the phospholipase A2 group VII (Pla2g7) gene, has been pertinent to inflammatory responses. This study investigates the correlation between Lp-PLA2 and inflammatory injury in septic mice and explores its regulatory mechanism. Lp-PLA2 was found to be upregulated in the serum of septic mice induced by cecal ligation and puncture and in the culture supernatant of RAW264.7 cells following lipopolysaccharide and adenosine triphosphate treatments. The contents of Lp-PLA2 were positively correlated with increased concentrations of proinflammatory cytokines in patients with sepsis. Both animal and cellular models showed increased concentrations of proinflammatory cytokines. Spi-1 proto-oncogene (Spi1), highly expressed in these models, was found to activate Pla2g7 transcription. Knockdown of Pla2g7 or Spi1 reduced the proinflammatory cytokine production, mitigated organ damage in mice, and suppressed macrophage migration in vitro. Retinoblastoma binding protein 6 (Rbbp6), poorly expressed in both models, was found to reduce Spi1 protein stability through ubiquitination modification. Rbbp6 overexpression similarly suppressed inflammatory activation of RAW264.7 cells, which was counteracted by Pla2g7 or Spi1 upregulation. In summary, this study demonstrates that the Pla2g7 loss and Spi1 upregulation participate in inflammatory responses in sepsis by elevating the Lp-PLA2 levels.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sepsis
/
1-Alquil-2-acetilglicerofosfocolina Esterasa
/
Inflamación
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Macrófagos
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Funct Integr Genomics
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA
Año:
2024
Tipo del documento:
Article