Galectin-3 regulates microglial activation and promotes inflammation through TLR4/MyD88/NF-kB in experimental autoimmune uveitis

Galectin-3, an attractive molecule of innate immunity, has been reported to be involved in the neuro-inflammatory diseases. However, the role of Galectin-3 in autoimmune uveitis is still unclear. The purpose of this study was to investigate the effect and mechanism of Galectin-3 on microglial activation and inflammation of experimental autoimmune uveitis (EAU). We immunized female C57BL/6 J mice with IRBP651-670 to induce EAU and the specific inhibitor was intravitreally injected in EAU mice. Disease severity was evaluated by clinical and histopathological scores. Immunofluorescence, western blot, qRT-PCR analysis and immunoprecipitation were used to detect the functional phenotypes and mechanisms on microglia after Galectin-3 inhibition. Our results showed that the expression of Galectin-3 was conspicuously increased in microglia of EAU retinas. The specific inhibitor of Galectin-3, TD139 was found to ameliorate the clinical and histological manifestations of EAU mice. In addition, TD139 reduced the expression of proinflammatory factors in vivo and vitro, which are related to the severity of uveitis. In mechanism, TD139 down-regulated the expression of TLR4 and MyD88, and then inhibited the activation of NF-kappa B p65 in microglia. In conclusion, Galectin-3 may play important roles in a variety of immune related diseases including autoimmune uveitis. Additionally, the inhibition of Galectin-3 may attenuate the microglial activation and inflammatory response through TLR4/MyD88/NF-kappa B pathway, highlighting a potential therapeutic target of Galectin-3 for autoimmune uveitis.

Automated summary

This study investigated the effect and mechanism of Galectin-3 on microglial activation and inflammation in autoimmune uveitis. The results showed that the expression of Galectin-3 was increased in microglia of uveitis retinas. Inhibition of Galectin-3 improved the clinical and pathological manifestations of uveitis and reduced the expression of proinflammatory factors. The mechanism involved down-regulation of TLR4 and MyD88 expression and inhibition of NF-kappa B p65 activation in microglia.