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.