IDO1 Reverses Macrophage Immunosenescence via Ammonia Metabolism Repression to ameliorate neuroinflammatory demyelination

1. IDO1 was applied to alleviated immunosenescence-induced inflammation in macrophage
The Figure 4G-1 (Hif-1α) and Figure 4G-2 (control) were rescue experiment results demonstrate that myelin debris activates the Hif-1α signaling pathway in macrophages through MSR1-mediated phagocytosis.
2. IDO1-Kyn inhibited Cth expression in dual mechanisms of Hif1a suppression
Western blot analyses confirmed that Hif-1α binds to recognition sites near the Cth gene promoter, promoting gene expression. This transcriptional regulation was suppressed by kynurenine. Figure 6H-1 (Hif-1α) and Figure 6H-2 (control). The senescent macrophage exhibited elevated Hif-1α level, which was markedly rescued by IDO1 treatment. Figure 6P-1(Hif-1α) and Figure 6P-2 (control).