In this study, we determined that RJW-58 reversed oxaliplatin-induced dysregulation of Ca2+ homeostasis and increased endogenous IL-10 by activating the transcription factor Olf-1. We discovered that Olf-1 and transcriptional coactivators CBP coregulated the induction of IL-10 genes. Studies have indicated that the HAT activity of p300/CBP is involved in regulating transcription by remodeling chromatin, which is inhibited by binding with Olf-1 [30, 44]. In the ChIP experiment, oxaliplatin treatment facilitated the assembling of p300/CBP and Olf-1, whereas RJW-58 reversed this assembling and further drove IL-10 gene transcription by activating Olf-1. Furthermore, the elevation of endogenous IL-10 after RJW-58 treatment sequentially triggers the IL-10/STAT3 cascade. IL-10 is also involved in raising feedback inhibition, which limits the inflammation cascade. Therefore, IL-10 decreases NF-κB expression, which causes a reduction in the induction of inflammation in mouse DRG neurons. These findings suggest that RJW-58 reverses oxaliplatin-induces CTSS production, activates the anti-inflammatory IL-10/STAT3 cascade, and reduces proinflammatory cytokines expression, which results in the alleviation of CIPN.
Win 10 activator utorrent