Apigenin Alleviates Autoimmune Uveitis by Inhibiting Microglia M1 Pro-Inflammatory Polarization

PURPOSE. Apigenin is a natural small molecule compound widely present in various vegetables and fruits. Recently, Apigenin was reported to inhibit lipopolysaccharide (LPS)-simulated microglial proinflammatory activation. Considering the important role of microglia in retinal disorders, we wonder whether Apigenin could exert a thera-peutic effect on experimental autoimmune uveitis (EAU) through reprogramming retinal microglia to a beneficial subtype. METHODS. EAU was induced in C57BL/6J mice by immunization with interphotorecep-tor retinoid-binding protein (IRBP)651-670, followed by intraperitoneal administration of Apigenin. Disease severity was assessed based on clinical and pathological scores. In vivo, Western blotting was used to quantify protein levels of classical inflammatory factors, microglial M1/M2 markers and the tight junction protein of the blood-retinal-barrier (BRB). Immunofluorescence was used to determine the Apigenin's efficacy on microglial phenotype. In vitro, Apigenin was added in LPS and IFN-& gamma; stimulated human microglial cell line. Western blotting and Transwell assays were used to analyze the phenotype of microglia. RESULTS. In vivo, we found that Apigenin significantly reduced the clinical and patho-logical scores of EAU. The protein levels of inflammatory cytokines were significantly decreased in retina, and BRB disruption was ameliorated after Apigenin treatment. Mean-while, Apigenin inhibited microglia M1 transition in EAU mice retina. In vitro functional studies showed that Apigenin decreased LPS and IFN-& gamma; -induced microglial inflammatory factor production and M1-activation via the TLR4/MyD88 pathway. CONCLUSIONS. Apigenin can ameliorate retinal inflammation in IRBP induced autoimmune uveitis through inhibiting microglia M1 pro-inflammatory polarization via TLR4/MyD88 pathway.

Automated summary

The purpose of this study was to investigate the therapeutic effect of Apigenin, a flavonoid compound, on experimental autoimmune uveitis (EAU). The results showed that Apigenin could ameliorate retinal inflammation by inhibiting microglia M1 pro-inflammatory polarization, thereby reducing the severity of the disease.