SP1 and central nervous system cancer: Sozen et al. (2009) reported that IL-1β antagonists reduce MMP-9 via c-Jun N-terminal kinase and protect BBB integrity after SAH. In glioma cells, TNF-α induces VEGF expression via the transcription factor SP-1 (Ryuto et al., 1996). Chen et al. (2014a) reported that melatonin protects BBB integrity by reducing the expression of MMP-9 and VEGF, which is regulated by inflammatory cytokines (TNF-α, IL-6, and IL-1β), thereby reducing the brain edema induced by the inflammatory responses after SAH.