Lipocalin-2 Deficiency Diminishes Canonical NLRP3 Inflammasome Formation and IL-1ß Production in the Subacute Phase of Spinal Cord Injury.
Int J Mol Sci
; 24(10)2023 May 12.
Article
em En
| MEDLINE
| ID: mdl-37240031
ABSTRACT
Spinal cord injury (SCI) results in the production of proinflammatory cytokines due to inflammasome activation. Lipocalin 2 (LCN2) is a small secretory glycoprotein upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 secretion is induced by infection, injury, and metabolic disorders. In contrast, LCN2 has been implicated as an anti-inflammatory regulator. However, the role of LCN2 in inflammasome activation during SCI remains unknown. This study examined the role of Lcn2 deficiency in the NLRP3 inflammasome-dependent neuroinflammation in SCI. Lcn2-/- and wild-type (WT) mice were subjected to SCI, and locomotor function, formation of the inflammasome complex, and neuroinflammation were assessed. Our findings demonstrated that significant activation of the HMGB1/PYCARD/caspase-1 inflammatory axis was accompanied by the overexpression of LCN2 7 days after SCI in WT mice. This signal transduction results in the cleaving of the pyroptosis-inducing protein gasdermin D (GSDMD) and the maturation of the proinflammatory cytokine IL-1ß. Furthermore, Lcn2-/- mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis, IL-1ß production, pore formation, and improved locomotor function compared with WT. Our data suggest that LCN2 may play a role as a putative molecule for the induction of inflammasome-related neuroinflammation in SCI.
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Bases de dados:
MEDLINE
Assunto principal:
Traumatismos da Medula Espinal
/
Proteína HMGB1
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha