Upregulation of TIPE2 attenuates macrophage activation and neuroinflammation after intracerebral hemorrhage in mice

Abstract

Background: Intracerebral hemorrhage (ICH) is a serious disease with high mortality and morbidity, and effective treatment is limited. A large amount of evidence suggests that the inflammatory response contributes to secondary brain damage following ICH. TIPE2 is an essential negative regulator of both innate and adaptive immunity, and depletion of TIPE2 causes inflammatory disease. However, the possible role of TIPE2 following ICH has not been reported. Methods: In this study, we investigated TIPE2 levels and inflammation in macrophages treated with erythrocyte lysate in vitro, and we observed proinflammatory cytokine production, BBB disruption, cerebral water content and neurological damage in ICH mice in vivo. Results: We found that TIPE2 levels were significantly decreased in erythrocyte lysate-treated macrophages compared to control macrophages. Upregulation of TIPE2 decreased macrophage activation and cytokine production and accelerated brain damage in ICH mice. In addition, upregulation of TIPE2 attenuated proinflammatory cytokine production, BBB disruption, and severe brain inflammation after ICH. Conclusion: The results demonstrated that TIPE2 was negatively correlated with the pathogenesis of ICH, which prevented brain injury and attenuated deleterious inflammatory responses following ICH. TIPE2 might serve as a novel target for ICH therapy.