1. Lipocalin-2 Deficiency Diminishes Canonical NLRP3 Inflammasome Formation and IL-1β Production in the Subacute Phase of Spinal Cord Injury.
- Author
-
Müller, Nina, Scheld, Miriam, Voelz, Clara, Gasterich, Natalie, Zhao, Weiyi, Behrens, Victoria, Weiskirchen, Ralf, Baazm, Maryam, Clarner, Tim, Beyer, Cordian, Sanadgol, Nima, and Zendedel, Adib
- Subjects
- *
SPINAL cord injuries , *NLRP3 protein , *INFLAMMASOMES , *LIPOCALIN-2 , *LIPOCALINS , *TOLL-like receptors - 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-1β. Furthermore, Lcn2−/− mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis, IL-1β 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF