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Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.
Xu, Hao-Jie; Lin, Ying-Yi; Yu, Jian-Jun; Zhang, Na; Hu, Jia-Min; Qu, Jin-Shuang; Yuan, Chao-Mei; Chen, Da-Qiu; Liang, Min; Cai, Hong-da; Zeng, Kai.
Afiliación
  • Xu HJ; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Lin YY; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Yu JJ; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Zhang N; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Hu JM; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Qu JS; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Yuan CM; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Chen DQ; Department of Cardiology, Affiliated Nanping First Hospital, Fujian Medical University, Nanping, 353000, Fujian Province, China.
  • Liang M; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Cai HD; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
  • Zeng K; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Institute of Anesthesiology
Eur J Pharmacol ; 976: 176665, 2024 Aug 05.
Article en En | MEDLINE | ID: mdl-38797312
ABSTRACT

OBJECTIVE:

Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation.

METHODS:

C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA.

RESULTS:

GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16.

CONCLUSIONS:

Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / FN-kappa B / Microglía / Sepsis / Giberelinas / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / FN-kappa B / Microglía / Sepsis / Giberelinas / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos