Lipocalin-2 Deﬁciency Diminishes Canonical NLRP3 Inﬂammasome Formation and IL-1β Production in the Subacute Phase of Spinal Cord Injury

Int. J. Mol. Sci., 2023 · DOI: 10.3390/ijms24108689 · Published: May 12, 2023

Simple Explanation

Spinal cord injury (SCI) leads to inﬂammation and the release of harmful substances. Lipocalin-2 (LCN2) is a protein that can be involved in both promoting and reducing inﬂammation. This study investigates LCN2's role in inﬂammation after SCI. The researchers found that LCN2 increases in the spinal cord after injury, contributing to the activation of inﬂammasomes, which are key components of the inﬂammatory response. Mice lacking LCN2 showed less inﬂammation and better recovery after SCI. These findings suggest that LCN2 may be a potential target for therapies aimed at reducing inﬂammation and improving outcomes after spinal cord injury.

Study Duration

Not specified

Participants

Lcn2−/− and wild-type (WT) mice

Evidence Level

Not specified

Key Findings

1
Significant activation of the HMGB1/PYCARD/caspase-1 inflammatory axis was observed 7 days after SCI in WT mice, accompanied by LCN2 overexpression.
2
Lcn2−/− mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis and IL-1β production compared with WT mice.
3
Lcn2 deficiency significantly improved locomotor function after SCI, indicating better functional recovery.

Research Summary

This study investigated the role of LCN2 in NLRP3 inflammasome-dependent neuroinflammation following spinal cord injury (SCI) using Lcn2−/− mice. The findings demonstrate that LCN2 enhances inflammatory responses after SCI by inducing the priming and activation of the inflammasome and its components. Lcn2 deficiency improves functional recovery and attenuates inflammatory responses after SCI, suggesting LCN2 as a potential therapeutic target.

Practical Implications

Therapeutic Target

Neutralizing LCN2 with specific antibodies may reduce inflammation and enhance patient outcomes after SCI.

Neuroinflammation Management

Understanding the mechanisms attributed to secondary injury, like the role of LCN2, is critical for reducing future damage and providing a better environment for recovery.

Gut-Brain Axis Study

A prospective study is recommended to assess the role of the gut–brain axis in managing SCI acute inflammation with the central role of LCN2.

Study Limitations

1
Study used only male mice, limiting generalizability to females.
2
The relationship between LCN2 and NLRP3 is indirect; further studies are needed to clarify a correlation.
3
NLRP3-independent pathways may contribute to the differences observed in IL-1β secretion and CASP1 activation.

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