| First Author | Müller N | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 10 | PubMed ID | 37240031 |
| Mgi Jnum | J:355749 | Mgi Id | MGI:7487240 |
| Doi | 10.3390/ijms24108689 | Citation | Muller N, et al. (2023) Lipocalin-2 Deficiency Diminishes Canonical NLRP3 Inflammasome Formation and IL-1beta Production in the Subacute Phase of Spinal Cord Injury. Int J Mol Sci 24(10) |
| abstractText | 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-1beta. Furthermore, Lcn2(-/-) mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis, IL-1beta 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. |
