TRIM55 suppresses inflammatory response after spinal cord injury by accelerating the ubiquitination and degradation of TLR4.

BACKGROUND

Spinal cord injury (SCI) is a neurological disorder characterized by severe and often irreversible damage to the spinal cord, for which no effective treatments currently exist. Ubiquitination, a reversible post-translational modification, plays a critical role in regulating protein degradation and stabilization. Tripartite motif-containing 55 (TRIM55), an E3 ubiquitin ligase, belongs to the TRIM protein family. This study aimed to explore the potential mechanism of TRIM55 in SCI.

METHODS

An SCI rat model was established to investigate the effects of TRIM55 on SCI. LPS-stimulated PC12 cells were used to evaluate inflammation by measuring IL-1β, IL-6, and TNF-α levels using enzyme-linked immunosorbent assays. The proliferation and apoptosis of PC12 cells were assessed using the cell counting kit-8 assay and TUNEL staining. Quantitative real-time PCR, western blot analysis, co-immunoprecipitation, and cycloheximide chase experiments were performed to elucidate the underlying mechanism.

RESULTS

The findings revealed that TRIM55 was downregulated both in vitro and in vivo. Functionally, TRIM55 inhibited apoptosis and reduced the expression of pro-inflammatory cytokines in LPS-stimulated PC12 cells. Mechanistically, TRIM55 interacted with toll-like receptor 4 (TLR4) and promoted its degradation by modulating the ubiquitination process, thereby attenuating the inflammatory response. Furthermore, TRIM55 enhanced recovery from SCI and alleviated inflammation in vivo.

CONCLUSION

This study not only provides robust theoretical evidence supporting TRIM55 as an anti-inflammatory factor but also offers a novel therapeutic approach for SCI research.