PU.1 interaction with p50 promotes microglial-mediated inflammation in secondary spinal cord injury in SCI rats.

Secondary spinal cord injury is the inflammatory damage to surrounding tissues caused by activated microglial-mediated neuroinflammatory responses. The nuclear factor-κB (p65/p50) pathway and PU.1 are closely correlated with inflammatory responses; thus, we examined the relationship and function between PU.1 and p50 in secondary spinal cord injury. In this study, we established an adult rat acute spinal cord injury model to simulate the pathological process of spinal cord injury.: We found that the expression of PU.1 was significantly increased at three days after spinal cord injury and mainly expressed in activated microglia. Moreover, p-p50 expression was increased in SCI rats and the protein interacted with PU.1. Lipopolysaccharide was used to induce microglia activation in vitro.: The results showed that PU.1 and p-p50 expression was significantly increased and PU.1 interacted with p50 in the nucleus. The levels of tumor necrosis factor-α and interleukin-1β secreted by microglia were detected by enzyme-linked immunosorbent assay. The results showed that when both PU.1 and p50 were overexpressed, tumor necrosis factor-α and interleukin-1β secretion was significantly increased to levels higher than in cells overexpressing PU.1 or p50 alone. These results suggest that PU.1 and p50 interact to promote p65 transcription and the expression of inflammatory factors, which is an important mechanism of the microglial-mediated inflammatory response to secondary injury after spinal cord injury.